Strobilurin formulations

ABSTRACT

The present disclosure describes a formulation including a nanoparticle including a polymer-associated strobilurin compound with an average diameter of between about 1 nm and about 500 nm; wherein the polymer is a polyelectrolyte, and a dispersant or a wetting agent. The disclosure describes various formulations and formulating agents that can be included in the formulations. Additionally, the disclosures describes application to various plants and fungi as well as advantages of the disclosed formulations.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.14/367,473, filed on Jun. 20, 2014 (now issued as U.S. Pat. No.10,206,391), which is a national stage entry of InternationalApplication No. PCT/IB2012/002118, filed Aug. 23, 2012, which claimspriority to U.S. Provisional Patent Application No. 61/578,983, filed onDec. 22, 2011, the entire contents of each of which are herebyincorporated by reference.

BACKGROUND

Strobilurins are widely used in agriculture as fungicides. They belongto the Q_(o)I_(family) family of fungicides and are used to control awide array of fungal diseases caused by water moulds, downy mildews,powdery mildews, leaf spotting and blighting fungi, fruit rotters, andrusts. Q_(o)I fungicides are chemical compounds that act at the Quinolouter binding site of the cytochrome bc1 complex, inhibiting fungalmitochondrial respiration that stops energy production in the fungus andresults in its death. The strobilurins are used on a wide variety ofcrops including cereals, field crops, fruits, tree nuts, vegetables,turfgrass and ornamentals. Most strobilurins show weak systemicactivity, and are useful—to varying degrees—as protectant, curative andtranslaminar fungicides (ref: Balba, H. J. Envi. Sci. Heath. Part B.2007, 42, 441. As an example, azoxystrobin shows good protective yetmild curative properties due to its weak systemic properties. A usefulformulation would mitigate these drawbacks of the fungicide and ideallyprovide excellent protectant and curative properties, so that it canboth protect a crop from fungal infection and eradicate the infectionafter it is established. Because strobilurins target only a singlemetabolic pathway in the fungus, there are instances where mutations canoccur in certain species that can make them resistant to strobilurins.It is therefore also useful to create strobilurin formulations that caneasily be mixed with fungicides that have other modes of action tominimize the spread of strobilurin resistant strains.

Strobilurins are nonpolar compounds, have relatively low watersolubility (on the scale of ug/L-g/L), low volatility, and have moderateto low soil mobility. Strobilurins can vary in their stability towardshydrolysis and photolysis under natural environmental conditions wherepH and temperature contribute to their chemical degradation. There isfurther a need to create formulations that can extend the effectivelifetime of strobilurins and related compounds by reducing theirsusceptibly towards chemical degradation both before and after theformulation has been applied in the field.

Strobilurins are currently formulated into various usable forms such asemulsifiable concentrates (ECs), liquid concentrate (SL), and suspensionconcentrates (SC) that use petroleum or non-petroleum based solventsalong with anionic and non-ionic emulsifiers and stabilizers.Strobilurins have also been formulated as water dispersible powders orgranules (WPs or WGs) and soluble powders (SP) that use organic orinorganic carriers. These formulations are available as solid or liquidformulations with varying contents of active ingredient (low or high)that can be used as is or after dilution with water. As described below,while these formulations address some of the inherent challenges thatare associated with strobilurins there remains a need in the art forimproved strobilurin formulations.

SUMMARY OF THE INVENTION

The present disclosure provides formulations of strobilurin compoundsincluding nanoparticles of polymer-associated strobilurin compoundsalong with various formulating agents. The present disclosure alsoprovides methods for producing and using these formulations.

In various embodiments of the present disclosure presents formulationsincluding a nanoparticle including a polymer-associated strobilurincompound with an average diameter of between about 1 nm and about 500nm; and the polymer is a polyelectrolyte, and a dispersant or a wettingagent.

In some embodiments, the nanoparticle has a diameter of between about 1nm and about 100 nm. In some embodiments, the nanoparticle has adiameter of between about 1 nm and about 20 nm.

In some embodiments, the formulation includes a plurality ofnanoparticles, wherein the nanoparticles are in an aggregate and theaggregate has a diameter of between about 10 nm and about 5000 nm. Insome embodiments, the formulation includes a plurality of nanoparticles,wherein the nanoparticles are in an aggregate and the aggregate has adiameter of between about 100 nm and about 2500 nm. In some embodiments,the formulation includes a plurality of nanoparticles, wherein thenanoparticles are in an aggregate and the aggregate has a diameter ofbetween about 100 nm and about 1000 nm. In some embodiments, theformulation includes a plurality of nanoparticles, wherein thenanoparticles are in an aggregate and the aggregate has a diameter ofbetween about 100 nm and about 300 nm.

In some embodiments the ratio of strobilurin compound to polymer withinthe nanoparticles is between about 10:1 and about 1:10 on a w/w basis.In some embodiments, the ratio of strobilurin compound to polymer withinthe nanoparticles is between about 5:1 and about 1:5. In someembodiments, the ratio of strobilurin compound to polymer within thenanoparticles is between about 2:1 and about 1:2. In some embodiments,the ratio of strobilurin compound to polymer within the nanoparticles isabout 1:3. In some embodiments, the ratio of strobilurin compound topolymer within the nanoparticles is about 3:2. In some embodiments, theratio of strobilurin compound to polymer within the nanoparticles isabout 1:1. In some embodiments, the ratio of strobilurin compound topolymer within the nanoparticles is about 4:1. In some embodiments, theratio of strobilurin compound to polymer within the nanoparticles isabout 2:1.

In some embodiments, the strobilurin compound is azoxystrobin. In someembodiments, the strobilurin compound is pyraclostrobin. In someembodiments, the strobilurin compound is trifloxystrobin.

In some embodiments, the polymer is selected from the group consistingof poly(methacrylic acid-co-ethyl acrylate); poly(methacrylicacid-co-styrene); poly(methacrylic acid-co-butylmethacrylate);poly[acrylic acid-co-poly(ethylene glycol) methyl ether methacrylate];poly(n-butylmethacrylcate-co-methacrylic acid). In some embodiments, thepolymer is a homopolymer. In some embodiments, the polymer is acopolymer. In some embodiments, the polymer is a random copolymer.

In some embodiments, the dispersant and/or wetting agent is selectedfrom the group consisting of lignosulfonates, organosilicones,methylated or ethylated seed oils, ethoxylates, sulfonates, sulfates andcombinations thereof. In some embodiments, the dispersant and/or wettingagent is sodium lignosulfonate. In some embodiments, the dispersantand/or wetting agent is a tristyrylphenol ethoxylate. In someembodiments, the wetting agent and the dispersant are the same compound.In some embodiments, the wetting agent and the dispersant are differentcompounds.

In some embodiments, the formulation excludes any wetting agent. In someembodiments, the formulation excludes any dispersant. In someembodiments, the wetting agent is less than about 30 weight % of theformulation. In some embodiments, the wetting agent is less than about 5weight % of the formulation. In some embodiments, the dispersant is lessthan about 30 weight % of the formulation. In some embodiments, thedispersant is less than about 5 weight % of the formulation.

In some embodiments, the formulation is in the form of a high solidsliquid suspension.

In some embodiments, the formulation includes between about 0.05 weight% and about 5 weight % of a thickener. In some embodiments, thethickener is less than about 1 weight % of the formulation. In someembodiments, the thickener is less than about 0.5 weight % of theformulation. In some embodiments, the thickener is less than about 0.1weight % of the formulation. In some embodiments, the thickener isselected from the group consisting of guar gum; locust bean gum; xanthangum; carrageenan; alginates; methyl cellulose; sodium carboxymethylcellulose; hydroxyethyl cellulose; modified starches; polysaccharidesand other modified polysaccharides; polyvinyl alcohol; glycerol alkyd,fumed silica and combinations thereof.

In some embodiments, the formulation includes between about 0.01 weight% and about 0.2 weight % of a preservative. In some embodiments, thepreservative is less than about 0.1 weight % of the formulation. In someembodiments, the preservative is less than about 0.05 weight % of theformulation. In some embodiments, the preservative is selected from thegroup consisting of tocopherol, ascorbyl palmitate, propyl gallate,butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT),propionic acid and its sodium salt; sorbic acid and its sodium orpotassium salts; benzoic acid and its sodium salt; p-hydroxy benzoicacid sodium salt; methyl p-hydroxy benzoate; 1,2-benzisothiazalin-3-one,and combinations thereof.

In some embodiments, the formulation includes between about 0.05 weight% and about 10 weight % of an anti-freezing agent. In some embodiments,the anti-freezing agent is less than about 5 weight % of theformulation. In some embodiments, the anti-freezing agent is less thanabout 1 weight % of the formulation. In some embodiments, theanti-freezing agent is selected from the group consisting of ethyleneglycol; propylene glycol; urea and combinations thereof.

In some embodiments, the formulation includes water or PBS buffer. Insome embodiments, the water or PBS buffer is less than about 50 weight %of the formulation. In some embodiments, the water or PBS buffer is lessthan about 25 weight % of the formulation. In some embodiments, thewater or PBS buffer is less than about 10 weight % of the formulation.

In some embodiments, the polymer-encapsulated strobilurin compound isless than about 80 weight % of the formulation. In some embodiments, thenanoparticles of polymer-associated strobilurin comprise between about20 weight % and about 80 weight % of the formulation. In someembodiments, the nanoparticles of polymer-associated strobilurincomprise between about 20 weight % and about 60 weight % of theformulation. In some embodiments, the nanoparticles ofpolymer-associated strobilurin comprise about 20 weight % and about 50weight % of the formulation. In some embodiments, the nanoparticles ofpolymer-associated strobilurin comprise between about 25 weight % andabout 50 weight % of the formulation. In some embodiments, thenanoparticles of polymer-associated strobilurin comprise about 30 weight% and about 40 weight % of the formulation.

In some embodiments, the polymer-associated strobilurin compound isbetween about 5 weight % and about 40 weight % of the formulation. Insome embodiments, wherein the polymer-associated strobilurin compound isbetween about 5 weight % and about 25 weight % of the formulation. Insome embodiments, the polymer-associated strobilurin compound is betweenabout 10 weight % and about 25 weight % of the formulation. In someembodiments, the polymer-associated strobilurin compound is betweenabout 15 weight % and about 25 weight % of the formulation.

In various embodiments of the present disclosure presents formulationsincluding a nanoparticle including a polymer-associated strobilurincompound with an average diameter of between about 1 nm and about 500nm; and the polymer is a polyelectrolyte, a dispersant or a wettingagent, a thickener, a preservative, an anti-freezing agent; and water orPBS buffer.

In various embodiments of the present disclosure presents formulationsincluding a nanoparticle including a polymer-associated strobilurincompound with an average diameter of between about 1 nm and about 500nm; and the polymer is a polyelectrolyte, between about 1 weight % andabout 30 weight % of a dispersant or a wetting agent, between about 0.05weight % and about 5 weight % of a thickener, between about 0.01 weight% and about 0.2 weight % of a preservative, between about 0.05 weight %and about 10 weight % of an anti-freezing agent; and water or PBSbuffer.

In some embodiments, the nanoparticles of polymer-associated strobilurincomprise between about 20 weight % and about 80 weight % of the specificformulation described above. In some embodiments, the polymer-associatedstrobilurin compound is between about 5 weight % and about 25 weight %of the specific formulation described above.

In some embodiments, the formulation is in the form of a wettablegranule.

In some embodiments, the formulation includes an inert filler. In someembodiments, the inert filler makes up less than about 90 weight % ofthe formulation. In some embodiments, the inert filler makes up lessthan about 40 weight % of the formulation. In some embodiments, theinert filler makes up less than about 5 weight % of the formulation. Insome embodiments, the inert filler is selected from the group consistingof saccharides, celluloses, starches, carbohydrates, vegetable oils,protein inert fillers, polymers and combinations thereof.

In some embodiments, the formulation includes water. In someembodiments, the water is less than about 50 weight % of theformulation. In some embodiments, the water is less than about 25 weight% of the formulation. In some embodiments, the water is less than about10 weight % of the formulation.

In some embodiments, the formulation includes between about 1 weight %and about 20 weight % of a disintegrant. In some embodiments, thedisintegrant is selected from the group consisting of polyvinylpyrrolidone, modified cellulose gum, pregelatinized starch, cornstarch,modified corn starch, sodium carboxymethyl starch, microcrystallinecellulose, sodium starch glycolate, sodium carboxymethyl cellulose,carmellose, carmellose calcium, carmellose sodium, croscarmellosesodium, carmellose calcium, carboxymethylstarch sodium, low-substitutedhydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxypropylcellulose, soy polysaccharides, alkylcelullose, hydroxyalkylcellulose,alginates, dextrans and poly(alkylene oxide), a combination of citricacid or bicarbonate, a combination of ascorbic acid and bicarbonate,lactose, anhydrous dibasic calcium phosphate, dibasic calcium phosphate,magnesium aluminometasilicate, synthesized hydrotalcite, silicicanhydride synthesized aluminum silicate and combinations thereof.

In some embodiments, the polymer-associated strobilurin compound has amelting point of less than 100° C. In some embodiments, thepolymer-associated strobilurin compound has a melting point of less than80° C. In some embodiments, polymer-associated strobilurin compound isselected from the group consisting of the following picoxystrobin,pyraclostrobin, orysastrobin, metominostrobin and trifloxystrobin.

In some embodiments, the formulation excludes a UV-blocker. In someembodiments, the formulation excludes a thickener.

In some embodiments, the formulation includes between about 1 weight %and about 20 weight % of a non-ionic surfactant. In some embodiments,the non-ionic surfactant is less than about 1 weight % of theformulation. In some embodiments, the non-ionic surfactant is less thanabout 0.5 weight % of the formulation. In some embodiments, thenon-ionic surfactant is selected from the group consisting ofalkylphenol ethoxylates, tristyrylphenol ethoxylates, aliphatic alcoholethoxylates, aliphatic alkylamine ethoxylates, sorbitan esters and theirethoxylates, castor oil ethoxylates, ethylene oxide/propylene oxidecopolymers, polymeric surfactants and combinations thereof.

In some embodiments, the formulation includes between about 0.1 weight %and about 90 weight % of a solvent. In some embodiments, the solvent isless than about 20 weight % of the formulation. In some embodiments, thesolvent is less than about 10 weight % of the formulation. In someembodiments, the solvent is selected from the group consisting ofalcohols, alkenes, alkanes, alkynes, phenols, hydrocarbons, chlorinatedhydrocarbons, ketones, water, ethers and combinations thereof.

In some embodiments, the formulation includes between about 0.05 weight% and about 5 weight % of an anti-foaming agent. In some embodiments,the anti-foaming agent is less than about 1 weight % of the formulation.In some embodiments, the anti-foaming agent is selected from the groupconsisting of sodium or ammonium phosphates, sodium carbonate orbicarbonate, sodium acetate, sodium metasilicate, magnesium or zincsulfates, magnesium hydroxide hydrates of any of the forgoing, sodiumalkylsulfosuccinates, silicious compounds, magnesium compounds, C10-C22fatty acids, polyvalent metal salt compounds and combinations thereof.

In some embodiments, the formulation includes between about 0.05 weight% and about 3 weight % of an anti-caking agent. In some embodiments, theanti-caking agent is less than about 1 weight % of the formulation. Insome embodiments, the anti-caking agent is selected from the groupconsisting of attapulgite clay, kieselguhr, silica aerogel, silicaxerogel, perlite, talc, vermiculite, sodium aluminosilicate, zirconiumoxychloride, starch, sodium or potassium phthalate, calcium silicate,calcium phosphate, calcium nitride, aluminum nitride, copper oxide,magnesium carbonate, magnesium silicate, magnesium nitride, magnesiumphosphate, magnesium oxide, magnesium nitrate, magnesium sulfate,magnesium chloride, and the magnesium and aluminum salts of C 10-C22fatty acids, refined kaolin clay, amorphous precipitated silica dioxide,refined clay, fumed silica, and combinations thereof.

In some embodiments, the formulation is diluted so that theconcentration of the polymer-associated strobilurin compound is betweenabout 0.1 to about 1000 ppm. In some embodiments, the formulation isdiluted so that the concentration of the polymer-associated strobilurincompound is between about 10 to about 1000 ppm. In some embodiments, theformulation is diluted so that the concentration of thepolymer-associated strobilurin compound is between about 10 to about 500ppm. In some embodiments, the formulation is diluted so that theconcentration of the polymer-associated strobilurin compound is betweenabout 10 to about 100 ppm.

In some embodiments, the formulation is in an aqueous dispersion. Insome embodiments, the formulation is the concentration of thestrobilurin in the dispersion is less than solubility limit of thestrobilurin in water. In some embodiments, the strobilurin is associatedwith the polymer in the dispersion.

In some embodiments, the water used to form the dispersion has an ionicstrength of between about 0 to about 8000 ppm calcium +2 equivalent. Insome embodiments, the water used to form the dispersion has an ionicstrength of between about 100 to about 2000 ppm calcium +2 equivalent.In some embodiments, the water used to form the dispersion has an ionicstrength of between about 100 to about 400 ppm calcium +2 equivalent. Insome embodiments, the water used to form the dispersion has an ionicstrength of between about 50 to about 400 ppm calcium +2 equivalent. Insome embodiments, the water used to form the dispersion has an ionicstrength of between about 1000 to about 4000 ppm calcium +2 equivalent.

In some embodiments, the aqueous dispersion further contains anherbicide. In some embodiments, the herbicide is glyphosate.

In some embodiments, the formulation further includes a fertilizer. Insome embodiments, the fertilizer is a liquid fertilizer. In someembodiments, the fertilizer comprises at least one of the elementsselected from the group consisting of the following: boron, copper,manganese, iron, chorine, molybdenum, zinc sulfur, nitrogen, phosphorusand potassium.

In some embodiments, the dispersion further includes between about 0.1weight % and about 20 weight % of a non-ionic surfactant. In someembodiments, the non-ionic surfactant is less than about 1 weight % ofthe formulation. In some embodiments, the non-ionic surfactant is lessthan about 0.5 weight % of the formulation. In some embodiments, thenon-ionic surfactant is selected from the group consisting ofalkylphenol ethoxylates, tristyrylphenol ethoxylates, aliphatic alcoholethoxylates, aliphatic alkylamine ethoxylates, sorbitan esters and theirethoxylates, castor oil ethoxylates, ethylene oxide/propylene oxidecopolymers, polymeric surfactants and combinations thereof.

In various aspect the present disclosure provides a method of using anyof the formulations described herein by applying the formulation to aplant.

In various embodiments of the present disclosure presents a method ofusing any of the formulations described above by applying theformulation to the root zone of a plant.

In various embodiments of the present disclosure presents a method ofusing any of the formulations described above by applying theformulation to one part of a plant and the strobilurin translocates toan unapplied part of the plant.

In some embodiments, the unapplied part of the plant includes new plantgrowth since the application.

In various embodiments of the present disclosure presents a method ofinoculating a plant with a strobilurin against fungi by applying any ofthe formulations described above to the plant's roots.

In some embodiments, the present disclosure provides a method oftreating a fungal infection of a plant with a strobilurin by applyingany formulation described herein to the plant.

In various embodiments of the present disclosure presents a method ofincreasing a plant's fungus resistance by applying any of theformulations described above to the plant's roots.

In some embodiments, the plant is selected from the classes fabaceaae,brassicaceae, rosaceae, solanaceae, convolvulaceae, poaceae,amaranthaceae, laminaceae and apiaceae.

In some embodiments, the plant is selected from oil crops, cereals,pasture, turf, ornamentals, fruit, legume vegetables, bulb vegetables,cole crops, tobacco, soybeans, cotton, sweet corn, field corn, potatoesand greenhouse crops.

In some embodiments, the fungi are selected from the classes ascomycota,basidiomycota, deuteromycota, blastocladiomycota, chytridiomycota,glomeromycota and combinations thereof.

In various embodiments of the present disclosure presents a method ofusing any of the formulations described above including the steps ofapplying any of the formulations described above to a crop field so thatthe concentration of the strobilurin is about at 0.35 grams per hectare.

In various embodiments of the present disclosure presents a method ofany of the formulations described above including the steps of applyingany of the formulations described above to trees, bushes or shrubs.

In some embodiments, the present disclosure provides a method of usingany of the formulations described herein by applying the formulation totrees, bushes or shrubs.

In various aspects the present disclosure provides a method of using anyformulation as described above to cure or prevent a fungal infection,and the formulation is applied to a soybean plant at a concentration ofbetween about 11 and about 109 grams of strobilurin compound per hectareand the fungus is selected from the group consisting of Aerial blight(Rhizoctonia solani), Anthracnose (Colletotrichum truncatum), Alternarialeaf spot (Alternaria spp.), Brown spot (Septoria glycines) Cercosporablight and leaf spot (Cercospora kikuchii), Frogeye leaf spot(Cercospora sojina), Pod and stem blight (Diaporthe phaseolorum). Insome embodiments, the strobilurin compound is azoxystrobin orpyraclostrobin.

In various aspects the present disclosure provides a method of using anyformulation as described above to cure or prevent a fungal infection,and the formulation is applied to a corn plant at a concentration ofbetween about 11 and about 109 grams of strobilurin compound per hectareand the fungus is selected from the group consisting of Rust (Pucciniasorghi), anthracnose leaf blight (Colletotrichum graminicola), Gray leafspot (Cercospora sorghi), Northern corn leaf blight (Setosphaeriaturcica), Northern corn leaf spot (Cochliobolus carbonum), Southern cornleaf blight (Cochliobolus heterostrophus) and Eye spot (Aureobasidiumzeae). In some embodiments, the strobilurin compound is azoxystrobin orpyraclostrobin.

In various aspects the present disclosure provides a method of using anyformulation as described above to cure or prevent a fungal infection,and the formulation is applied to a rice plant at a concentration ofbetween about 22 and about 228 grams of azoxystrobin per hectare and thefungus is selected from the group consisting of Aggregate sheath spot(Ceratobasidium oryzae-sativae, Rhizoctonia oryzae-sativae), Blacksheath rot (Gaeumannomyces graminis var. graminis), Sheath spot(Rhizoctonia oryzae), Stem rot (Magnaporthe salvinii=Sclerotiumoryzae=Nakateae sigmoidea), Brown leaf spot (Cochliobolus miyabeanus),Leaf smut (Entyloma oryzae), Narrow brown leaf spot (Cercosporajanseana=Cercospora oryzae), Kernel smut (Tilletia barclayana, Neovossiabarclayana) and Panicle blast (Pyricularia grisea).

In various aspects the present disclosure provides a method of using anyformulation as described above to cure or prevent a fungal infection,and the formulation is applied to a wheat plant at a concentration ofbetween about 5 and about 50 grams of azoxystrobin per hectare and thefungus is selected from the group consisting of Bipolaris sorokiniana,Drechslera tritici-repentis, and Puccinia triticina.

In various aspects the present disclosure provides a method of using anyformulation as described above to cure or prevent a fungal infection,and the formulation is applied to a wheat plant at a concentration ofbetween about 11 and about 110 grams of pyraclostrobin per hectare andthe fungus is selected from the group consisting of Black Spot, LeafRust, Powdery Mildew, Septoria Leaf And Glume Blotch, Spot Blotch, StemRust, Stripe Rust, and Tan Spot (Yellow Leaf Spot).

In various aspects the present disclosure provides a method of using anyformulation as described above to cure or prevent a fungal infection,and the formulation is applied to a wheat plant at a concentration ofbetween about 15 and about 150 grams of pyraclostrobin per hectare andthe fungus is selected from the group consisting of Drechesleratritici-repentis, Pucciniatriticina, Bipolaris sorokiniana,Leptosphaeria nodorum, and Septoria tritici.

In various aspects the present disclosure provides a method of using anyformulation as described above to cure or prevent a fungal infection,and the formulation is applied to a rice plant at a concentration ofbetween about 11 and about 139 grams of trifloxystrobilurin per hectareand the fungus is sheath blight (Rhizoctonia solani).

In various aspects the present disclosure provides a method of making ahigh solids liquid suspension formulation including the steps of millingnanoparticles of a polymer-associated strobilurin compound with, adispersant and/or wetting agent; and water.

In various aspects the present disclosure provides a method of making ahigh solids liquid suspension formulation including the steps of millingpolyelectrolyte nanoparticles with, a strobilurin compound, a dispersantand/or wetting agent; and water.

In various aspects the present disclosure provides a method of making awettable granule formulation including the steps of mixing driednanoparticles of a polymer-associated strobilurin compound with water,extruding the mixture through an orifice; and dividing the extrudedmaterial into granules.

In some embodiments, the strobilurin compound used in the method ofmaking described above has a melting point below 100° C. In someembodiments, the strobilurin compound used in the method of makingdescribed above has a melting point below 80° C.

In some embodiments, the strobilurin compound used in the method ofmaking described above is selected from the group consisting of thefollowing picoxystrobin, pyraclostrobin, orysastrobin, metominostrobinand trifloxystrobin.

In some embodiments, the strobilurin compound used in the method ofmaking described above is between about 5 weight % and about 25 weight %of the formulation.

In some embodiments, the strobilurin compound used in the method ofmaking described above is between about 10 weight % and about 25 weight% of the formulation.

In some embodiments, the strobilurin compound used in the method ofmaking described above is between about 15 weight % and about 25 weight% of the formulation.

In some embodiments, the polymer nanoparticles and the strobilurincompound used in the method of making described above is between about20 weight % and about 80 weight % of the formulation. In someembodiments, the polymer nanoparticles and the strobilurin compound usedin the method of making described above is between about 20 weight % andabout 60 weight % of the formulation. In some embodiments, the polymernanoparticles and the strobilurin compound used in the method of makingdescribed above is between about 20 weight % and about 50 weight % ofthe formulation. In some embodiments, the polymer nanoparticles and thestrobilurin compound used in the method of making described above isbetween about 30 weight % and about 50 weight % of the formulation.

In some embodiments, the ratio of strobilurin compound to polymer withinthe nanoparticles used in the methods of making described above isbetween about 5:1 and about 1:5.

In some embodiments, the method of making described above includes oneor more of the following formulating agents: an anti-freeze, aanti-foaming agent, a thickener, a preservative.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 shows the results of Differential Scanning Calorimetry (DSC)analysis of unformulated azoxystrobin and nanoparticles of polymerassociated azoxystrobin.

DEFINITIONS

As used herein, the term “inoculation” refers to a method used toadminister or apply a formulation of the present disclosure to a targetarea of a plant or fungus. The inoculation method can be, but is notlimited to, aerosol spray, pressure spray, direct watering, and dipping.Target areas of a plant could include, but are not limited to, theleaves, roots, stems, buds, flowers, fruit, and seed. Target areas ofthe fungus could include, but are not limited to, the hyphae andmycelium, inoculating reproductive spores (conidia or ascospores) andthe haustoria. Inoculation can include a method wherein a plant istreated in one area (e.g., the root zone or foliage) and another area ofthe plant becomes protected (e.g., foliage when applied in the root zoneor new growth when applied to foliage). Inoculation can also include amethod wherein a plant is treated in one area (e.g., the foliar surface)and fungal infection in the interior of the plant is cured.

As used herein, the term “wettable granule” also referred to herein as“WG”, “wettable granule”, and “soluble granule” refers to a solidgranular formulation that is prepared by a granulation process and thatcontains nanoparticles of polymer-associated active ingredient,(includes potentially aggregates of the same), a wetting agent and/or adispersant, and optionally an inert filler. Wettable granules can bestored as a formulation, and can be provided to the market and/or enduser without further processing. In some embodiments, they can be placedin a water-soluble bag for ease of use by the end user. In mostpractical applications, wettable granules are prepared for applicationby the end user. The wettable granules are mixed with water in the enduser's spray tank to the proper dilution for the particular application.Dilution can vary by crop, fungus, time of year, geography, localregulations, and intensity of infestation among other factors. Onceproperly diluted, the solution can be applied by e.g., spraying.

As used herein, the term “wettable powder” also referred to herein as“WP”, “water dispersible powder” and “soluble powder”, refers to a solidpowdered formulation that contains nanoparticles of polymer-associatedactive ingredient (includes potentially aggregates of the same), andoptionally one or more of a dispersant, a wetting agent, and an inertfiller. Wettable powders can be stored as a formulation, and can beprovided to the market and/or end user without further processing. Insome embodiments, they can be placed in a water-soluble bag for ease ofuse by the end user. In practical applications, a wettable powder isprepared for application by the end user. The wettable powder is mixedwith water in the end user's spray tank to the proper dilution for theparticular application. Dilution can vary by crop, fungus, time of year,geography, local regulations, and intensity of infestation among otherfactors. Once properly diluted, the solution can be applied by e.g.,spraying.

As used herein, the term “high solids liquid suspension” also referredto herein as “HSLS” refers to a liquid formulation that containsnanoparticles of polymer nanoparticles associated with active ingredient(includes potentially aggregates of the same), a wetting agent and/or adispersant, an anti-freezing agent, optionally an anti-settling agent orthickener, optionally a preservative, and water. High solids liquidsuspensions can be stored as a formulation, and can be provided to themarket and/or end user without further processing. In most practicalapplications, high solids liquid suspensions are prepared forapplication by the end user. The high solids liquid suspensions aremixed with water in the end user's spray tank to the proper dilution forthe particular application. Dilution can vary by crop, fungus, time ofyear, geography, local regulations, and intensity of infestation amongother factors. Once properly diluted, the solution can be applied bye.g., spraying.

DESCRIPTION OF VARIOUS EMBODIMENTS OF THE INVENTION

Strobilurins represent a very important class of fungicide globally.Strobilurins are primarily used in agriculture to protect crops such ascereals, field crops, fruits, tree nuts, vegetables, turfgrass andornamentals because of their broad spectrum activity as well as (tovarying degrees) their activity against all three major groups of plantpathogenic fungi: Ascomycetes, Basidiomycetes, and Deuteromycetes.Strobilurins have found limited use outside agricultural applications(such as human and veterinary antifungal formulations).

Strobilurins as a chemical class are based on natural substancesisolated from wood-rotting mushroom fungi from the genera Strobilurus.Natural strobilurins break down rapidly in light and upon exposure toH₂O and are thus not reliable for disease control. They can also breakdown rapidly in the soil due to bacterial degradation (Biocatalysis andBiotransformation, V29 (4), 119-129). While synthetic analogs of naturalstrobilurins have been developed and have resulted in compounds that areless subject to breakdown, most of the synthetic strobilurins stillundergo photolysis and degradation upon direct exposure to sunlightand/or soil. Strobilurins, whether naturally occurring or synthesized,suffer from several major problems that make them challenging to use asfungicides. In particular, in addition to being potentially degradedunder aqueous conditions, strobilurins also have limited watersolubility, exhibit low soil mobility and show weak to moderate systemicand curative activity in plants without the addition of adjuvants. Inthis context, curative activity refers to the ability for thestrobilurin to treat fungal infection that has already been establishedin the plant. This typically requires the strobilurin to be at leastmoderately systemic, as it needs to penetrate through the plant cuticleand into the plant to the infected tissue. Furthermore, because ofstrobilurins have a very specific mode of action, targeted fungi canbecome resistant. Different formulation techniques have therefore beendeveloped in an attempt to address these deficiencies. An idealformulation would have adequate loading of the active ingredient, benon-odorous, non-caking, non-foaming, stable under extreme conditionsfor extended periods of time, disperse rapidly upon addition to a spraytank, be compatible with a range of secondary additives and otheragricultural products (fertilizer, pesticide, herbicide and otherformulations) added to a spray tank, pourable or flowable, and, forsolid formulations, be non-dusty (for solid formulations), and havesufficient/superior rainfast properties after application.

UV Stability

Current strobilurins vary in their susceptibility to sunlight andexhibit a wide range of half lives as shown in Table 1.

TABLE 1 Photolytic stability of some Strobilurins Strobilurin Photolyticstability Fluxastrobin DT₅₀ 3.8-4.1 days in sterile aqueous phosphatebuffer, pH 7; 19-22 days under solar summer conditions, Phoenix AZ, USAin June.⁺ Fenamidone Readily photodegraded under aqueous conditions.DT₅₀ 5.9 days (lab., aerobic)⁺ Azoxystrobin DT₅₀ for aqueous photolysis8.7 days, pH 7 Picoxystrobin DT₅₀ for aqueous photolysis 21 days, pH 7Enestroburin — Pyraclostrobin Photolysis DT₅₀ in water 1.7 days, pH 7Famoxadone DT₅₀ 4.6 days (pH 5), 1.9 days in water (pH 7) DimoxystrobinDT₅₀ for aqueous photolysis 30 days, pH 7 Metominostrobin Slightlyunstable to light Orysastrobin Photolysis DT₅₀ 0.8 days, pH 7Kresoxim-methyl Photolysis DT₅₀ 18.2 days, pH 7 Trifloxystrobin Aqueousphotolysis DT₅₀ 2.7 days (pH 7), 1.1 days (pH 5) — — ⁺The e-pesticidemanual, Ver. 5. British Crop Protection Council

Due to the tendency of some strobilurins to degrade in sunlight, moststrobilurin formulations can include inorganic UV-blockers like zinc,tin or iron oxides or an organic UV blocker such as1,2-dihydroxybenzophenone (European Patent EP1755841, WIPO PatentApplication WO/2010/115720, European Patent EP1697578). The addition ofUV-blockers into a formulation can complicate formulations, asUV-blockers need to be soluble or dispersible in the matrix in which theproduct is formulated. It would therefore be desirable to provideformulations that do not require UV-blockers and can prevent formulatedactives to a certain degree from being degraded by UV irradiation.

Hydrolysis/Stability

Strobilurins vary widely in their stability in different media. Most arequite stable in neutral to slightly basic/acidic conditions but becomeincreasingly susceptible to hydrolysis/degradation under alkalineconditions. Stability data for some strobilurins are provided in Table 2(taken from the e-pesticide manual, Ver. 5. British Crop ProtectionCouncil). Most strobilurins are degraded in the plant tissues, and onlyfour strobilurins (azoxystrobin, fluxastrobin, picoxystrobin,dimoxystrobin) are metabolically sufficiently stable in plants and showa pronounced xylem systemicity (Zelená V., Veverka K., 2007, PlantProtect. Sci. V 43, 151-156). Therefore it would be desirable to haveformulations that provide protection to the formulated actives frombeing degraded or hydrolyzed in aqueous conditions.

TABLE 2 Stability data of some strobilurins in different mediaStrobilurin Stability data Fluxastrobin Hydrolysis DT₅₀ > 1 y (pH 4, 7and 9, 50° C.); Fenamidone Hydrolysis DT₅₀ (25° C., sterile conditions)41.7 d (pH 4), 411 d (pH 7), 27.6 d (pH 9). Azoxystrobin Stable tohydrolysis at pH 5-7 and room temperature. Picoxystrobin Stable at pH 5and pH 7; DT₅₀ c. 15 d (pH 9, 50° C.) Enestroburin — PyraclostrobinStable >30 d (pH 5-7, 25° C.). Famoxadone In water with no light, DT₅₀41 d (pH 5), 2 d (pH 7), 0.0646 d (pH 9) (25° C.); in water with light,DT₅₀ 4.6 d (pH 5, 25° C.). Dimoxystrobin Stable >30 d in aqueoussolution at pH 4-9, 50° C. Metominostrobin Stable to heat, and to acidicand alkaline media. Orysastrobin Hydrolysis DT₅₀ > 365 d Kresoxim-methylHydrolysis DT₅₀ 34 d (pH 7), 7 h (pH 9); relatively stable at pH 5.Trifloxystrobin Hydrolysis DT₅₀ 27.1 h (pH 9), 11.4 w (pH 7); stable atpH 5 (all 20° C.)Solubility

Strobilurins are typically very poorly soluble in water, usually withparts per million (ppm) or lower level solubility. They have highersolubility in polar organic solvents such as acetone, methanol, oracetonitrile. See Table 3 for a list of typical strobilurins and theirsolubility in different common solvents (taken from the e-pesticidemanual, Ver. 5. British Crop Protection Council).

TABLE 3 Solubility of some exemplary strobilurins in common solvents andoctanol-water partition coefficients and melting temperaturesT_(melting) Strobilurin Solubility K_(OW) (° C.) Fluxastrobin water 2.56(unbuffered), 2.29 (pH 7) mg/l (20° C.). logP = 2.86 103-108° C. Indichloromethane >250, xylene 38.1, isopropanol (20° C.) 6.7, n-heptane0.04 (all in g/l, 20° C.). Fenamidone water 7.8 mg/l (20° C.). Inacetone 250, acetonitrile logP = 2.8 136.8° C. 86.1, dichloromethane330, methanol 43, n- (20° C.) octanol 9.7 (all in g/l, 20° C.).Azoxystrobin water 6 mg/l (20° C.). In hexane 0.057, n-octanol logP =2.5 116° C.; 1.4, methanol 20, toluene 55, acetone 86, ethyl (20° C.)(tech., acetate 130, acetonitrile 340, dichloromethane 400 114-116° C.)(all in g/l, 20° C.). Picoxystrobin water 3.1 mg/l (20° C.). In methanol96, 1,2- logP = 3.6 75° C. dichloroethane, acetone, xylene and ethylacetate (20° C.) >250 (all in g/l, 20° C.). Enestroburin Insoluble inwater. Very soluble in acetone, ether — — and chloroform. Pyraclostrobinwater 1.9 mg/l (20° C.). In n-heptane 3.7, logP = 3.99 63.7-65.2° C.isopropanol 30.0, octanol 24.2, olive oil 28.0, (20° C.) methanol 100.8,acetone, ethyl acetate, acetonitrile, dichloromethane and toluene >500(all in g/l, 20° C.). Famoxadone water 52 (unbuffered water, pH7.8-8.9), 243 (pH logP = 4.65 141.3-142.3° C. 5), 111 (pH 7), 38 (pH 9)(all in μg/l, 20° C.). In (pH 7) acetone 274, toluene 13.3,dichloromethane 239, hexane 0.048, methanol 10, ethyl acetate 125.0,n-octanol 1.78, acetonitrile 125 (all in g/l, 25° C.). Dimoxystrobinwater 4.3 (pH 5.7), 3.5 (pH 8.0) (both in mg/l, 20° C.). logP = 3.59138.1-139.7° C. In dichloromethane >250, DMF 200-250, (pH 6.5) acetone67-80, acetonitrile 50-57, ethyl acetate 33-40, toluene 20-25, methanol20-25, isopropanol, n-heptane, n-octanol and olive oil all <10 (all ing/l, 20° C.). Metominostrobin water 0.128 g/l (20° C.). Indichloromethane 1380, logP = 2.32 87-89° C. chloroform 1280, DMSO 940(all in g/l, 25° C.). (20° C.) Orysastrobin water 80.6 mg/l (20° C.).logP = 2.36 98.4-99.0° C. (20° C.) Kresoxim-methyl water 2 mg/l (20°C.). In n-heptane 1.72, methanol logP = 3.4 101.6-102.5° C. 14.9,acetone 217, ethyl acetate 123, (pH 7, 25° C.) dichloromethane 939 (allin g/l solvent, 20° C.). Trifloxystrobin water 610 μg/l (25° C.). Inacetone, logP = 4.5 72.9° C. dichloromethane and ethyl acetate >500,hexane (25° C.) 11, methanol 76, octanol 18, toluene 500 (all in g/l,25° C.).

Because strobilurins have such low water solubility they need to beformulated to disperse in water before they can be applied to a plant orfungus.

Soil Mobility

Most strobilurins are substantially immobile in soil and are unlikely tomove via leaching. It has been shown that for some strobilurins, closeto 85% of the fungicide actually remains in the application zone itselfeven after several hundred millimeters of rainfall (ref: Pest. Manag.Sci. 2009, 65: 1009-1014); however, although some of the degradationproducts (from hydrolysis, photolysis or microbial degradation) showincreased mobility, these are typically less toxic or effective atcontrolling fungi than the parent compound. Without wishing to be boundby any theory, the low soil mobility is thought to be primarily due tothe strobilurin's non-polar nature and lack of water solubility. Whenstrobilurins are dispersed in water they therefore have a tendency toassociate with natural organic matter found in soils and, once bound tothe top soil's organic matter, exhibit low mobility within thesurrounding soil matrix.

General information about specific strobilurin soil persistence and soilmobility can be found in literature (Pest. Manag. Sci (2009) 65:1009-1014; Environ. Monit. Assess (2010) 162: 219-224). This lack ofsoil mobility limits the fungi that can be targeted with strobilurins,especially some soil-borne fungi that may reside beneath the top soilarea such as R. solanyi for sugar beets (Journal of Sugar Beet Research,V41 (1-2), 17-36), M. poae and other patch-causing fungi in turf such asL. korrae and R. cerealis (University of Guelph Pest Diagnostic ClinicFact Sheet: Necrotic Ring Spot It would therefore be desirable toprovide strobilurin formulations that have moderate soil mobility toallow the active to penetrate in the soil matrix.

Plant Uptake and Weak Systemic Effect

Fungicides can either be contact, translaminar or systemic. Contactfungicides are not taken up into the plant tissue, and only protect theplant where the spray is deposited. Translaminar fungicides redistributethe fungicide from the upper, sprayed leaf surface to the lower,unsprayed surface of the same leaf. Systemic fungicides are taken up andredistributed through the xylem vessels to the upper parts of the plant.Systemic activity is necessary to provide curative performance for afungicide. Most strobilurin compounds are weakly systemic, and thus aremainly used as protectants. Further, some strobilurins are weaklytranslaminar and to a certain extent, weakly systemic (e.g., curative)fungicides. Strobilurins are known to be highly effective against sporegermination and early penetration of the host e.g., show goodpreventative activity, but once the fungus has started to grow insidethe leaf tissue, strobilurins have little (especially for weaklysystemic strobilurins) or no effect.

When the strobilurin is applied to the plant, most of the activeingredient is initially held on or within the waxy cuticle of the plantsurface. If the strobilurin is showing weak systemic activity, this isbecause the active ingredient penetrates into the underlying plant cells(translaminar movement) and also moves to local zones above the point ofuptake (local systemization via the xylem in the leaf). The uptake ofthe strobilurin into the cells of the leaf following application isdependent on several factors: the formulation type, active ingredientparticle size, the additives/adjuvants used in the formulation, theother active ingredients mixed in or with the formulation, the targetcrop (leaf type, surface, weathering and plant age) and environmentalfactors that influence the drying of the spray droplet (Paul Vincelli,2002. Q_(o)I (Strobilurin) Fungicides: Benefits and Risks. The PlantHealth Instructor. DOI:10.1094/PHI-1-2002-089-02.)

Strobilurins are also non-systemic from root uptake; that is, they donot get taken up from the root and distributed throughout the planttissue. This can be problematic, as it means that any plant tissue thatneeds to be protected by the strobilurin formulation needs to beefficiently covered during the application process (typically spray).Unfortunately, aerial spray or foliar spray is often non-uniform anddoes not lead to complete coverage of the exterior of the plant (e.g.,see Henriet and Baur, Bayer Crop Science Journal 62(2):243, 2009). Inaddition, as plants grow they develop new foliar tissue that was nottreated with the strobilurin and hence will not be protected from fungalinfection until the next application. The degree of system activity canbe demonstrated by evaluating the performance of the strobilurin forcurative activity; improvements in curative activity can be correlatedwith improvements in systemization.

If a strobilurin could be made more systemic through improvements informulation it would dramatically improve the impact of strobilurins ontarget crops because of the potentially reduced application rates andenhanced efficacy of such formulations.

Fungicide Resistance

All strobilurins are site specific fungicides and only block theelectron transfer at the site of quinol oxidation in the cytochrome bc₁complex—preventing ATP formation in the fungus which leads to itseventual death. Because the mode of action of strobilurins is highlyspecific, i.e., it targets only a single metabolic pathway in thefungus, there are instances where mutations can occur in certain fungalspecies that can make them resistant to strobilurins. If such aresistant strain occurs, repeated application of the strobilurin canlead to a buildup of a strobilurin-resistant subpopulation in an entirecrop/plantation. There are two types of fungicide resistance:quantitative and qualitative. Quantitatively resistant pathogens areless sensitive to the fungicide compared to the wild type, but can stillbe controlled with a higher use rate and/or more frequent applications.On the other hand, qualitatively resistant strains areinsensitive/unresponsive to the fungicide and can no longer becontrolled at labeled field rates. To slow the rate of proliferation ofresistant strains, it is useful to limit the consecutive applications ofstrobilurin fungicides to the earlier stages of fungal infection as wellas applying a second type of fungicide that possesses another mode ofaction. It is therefore useful to provide strobilurin formulations thatcan easily be mixed with another type of fungicide that has a differentmode of action to help reduce the risk of resistant strains. Inaddition, improved formulations that are more effective at lower rates,show longer-lasting activity, or can be applied less frequently due toimprovements in systemic activity can also decrease issues withresistance due to decreased application intervals.

Plant Health and Hidden Disease

Growers strive to obtain high yielding and high quality plants andcrops. Toward this goal, agricultural strategies are utilized tomaintain, optimize, and enhance plant health from the time of plantingthrough to harvest. As a descriptive term, plant health refers to theoverall condition of a plant, including its size, sturdiness, optimummaturity, consistency in growth pattern and reproductive activity.Growers often also define plant health in terms of measureable outputs,such as enhanced crop yield and economic return on production input.

As the effective control of fungal disease is of central importance inimproving and optimizing plant health and crop yield, strobilurinfungicides are often applied as part of regimes directed towardsachieving these results. Plant health applications of strobilurins mayinclude preventative inoculations to optimize disease control,inoculations for the purpose of combating hidden disease, inoculationsunder conditions that are favorable for the development of disease(e.g., favorable weather conditions), insurance applications, and otherapplications to improve crop yield and quality. For example,preventative applications of strobilurin fungicides, such asazoxystrobin, are often performed on row crops to prevent fungalinfections. Furthermore, environmental conditions are closely andconstantly monitored by growers, and upon tending towards circumstancesthat are favorable for fungal infections, strobilurin applications areperformed.

Of central importance to the improvement of plant health via theapplication of strobilurin fungicides is combating hidden or undiagnoseddisease. Growers have implicated hidden diseases (i.e., cases in whichthe crop has below detection limit or non-obvious fungal infection) inreduced and variable crop yields. In response, strobilurin fungicidesare often used in plant health applications such as insuranceapplications (e.g., applications that are made regardless of diseasepressure), particularly on high potential crops such as soybean andcorn. In many cases these have been found to reverse or dampen theeffects of hidden disease on crops and improve yield.

There are, however, persistent challenges related to the use ofstrobilurins in improving plant health by combating hidden disease, themost problematic of which are related to correct timing of applicationand low or insufficient levels of curative activity. For example, priorto early strobilurin applications (e.g., the first application of theseason), there is often a level of latent infection or hidden disease inthe crop. In such cases, commercial formulations that demonstratepreventative activity but that suffer from low or less than adequatelevels of curative activity would be ineffective at improving planthealth by combating hidden disease. To compensate in part for their lowcurative activity, commercial formulations are sometimes applied atincreased rates. Furthermore, plant physiology and pathology areextremely complex, and there remain unanswered questions surrounding theoptimal time points for application of fungicides to improve planthealth by combating hidden disease.

It would thus be desirable to develop strobilurin formulations thatprovide increased levels of curative activity for plant healthapplications, including the treatment of latent and hidden fungaldisease. For example, it would be useful to produce strobilurinformulations that have increased levels of curative activity byimparting systemic properties to a strobilurin or improving the systemicproperties of the fungicide. Such formulations would be more effectivein plant health applications and could therefore be used at lowereffective dose rates than currently available commercial formulations.Furthermore, it would be useful to provide strobilurin formulations thatcould in part mitigate the difficulties associated with correct timingof fungicide applications directed to improving plant health. Forexample, formulations that display enhanced residual activity wouldincrease the window of opportunity for successful application timing.

Formulations—Generally

Several synthetic strobilurins (including azoxystrobin, trifloxystrobin,pyraclostrobin, and kresoxim-methyl) formulations are now availablecommercially, and the bulk of which are used in agriculturalapplications. Despite a common mode of action, strobilurins exhibitdefinite practical differences, e.g., different mobility in the plant.As an example, azoxystrobin is weakly systemic; trifloxystrobin is notsystemic but can move to the other side of the leaf and can even affectsurrounding foliage (i.e., it is translaminar).

The aforementioned limitations of strobilurins, and their formulations,when used as fungicides manifest themselves in (a) how they arecurrently applied to plants and (b) how they are formulated bymanufacturers. As an example, because strobilurins are susceptible todegradation (either from photolysis, hydrolysis or exposure of fieldconditions) end users (e.g., farmers or golf course maintenancemanagers) need to apply strobilurins more often than if they were longerlasting. As another example, because strobilurins lack systemic activity(which would help protect new growth of crops), end users need tocontinually re-apply strobilurins in order to protect crops from fungalinfection. Similarly, strobilurins will also need to be re-applied incertain cases because some strobilurin formulations are not rainfast orsufficiently rainfast and may easily get washed off the foliage if heavyrainfall occurs soon after application. Furthermore, because of theinherent threat of forming strobilurin resistant strains, end users needstrobilurin formulations that that can easily be mixed with other typesof formulated fungicides as well as formulations that have improvedresidual activity (i.e., would need less applications). Theselimitations are compounded by increasing pressure on end users who arefaced with increasing regulatory and consumer pressure to use fewerpesticides and/or fungicides and in lower quantities.

In order to address these limitations, a variety of complicatedformulation techniques and formulation agents have been developed tocounter to the UV instability, water insolubility, non-systemic nature,and low soil mobility of strobilurins.

In order for a strobilurin to be efficiently applied to a plant orfungus, the strobilurin product needs to be dispersible in water. Thetwo most common formulation techniques to do this are to produce eitheran emulsifiable concentrate (EC) or a suspension concentrate (SC). An ECis a formulation where the active ingredient is dissolved in a suitablesolvent in the presence of surfactants. When the EC is dispersed intothe spray tank and agitated, the surfactants emulsify the solvent intowater, and the active ingredient is delivered in the solvent phase tothe plant or fungus. A SC is a high-solids concentrate in water. Theactive ingredient is milled into particles that are 1-10 microns (AlanKnowles, Agrow Reports: New Developments in Crop Protection ProductFormulation. London: Agrow Reports May 2005). These solid particles arethen dispersed into water at high concentration using surfactants. Afteradding the SC into the spray tank, the surfactant-stabilized particlesdisperse into water and are applied (still as solid particles) to theleaf surface. Other common formulation techniques used for some cropprotection active ingredients include microencapsulations (CS) andemulsions (EW or OW). Solid formulation techniques that are currentlyused include water-dispersible granules (WG) or powders (WP), where theactive ingredient is absorbed to a dispersible carrier that is provideddry to the farmer. When mixed into the spray tank, the carrier dispersesinto the water, carrying the active ingredient with it. Particle sizesfor these carriers can be anywhere in the range of 1-10 microns (AlanKnowles, Agrow Reports: New Developments in Crop Protection ProductFormulation. London: Agrow Reports May 2005).

As an alternative to these approaches, we have developed new classesstrobilurin formulations. As demonstrated in the Examples and asdiscussed below, in some embodiments these new strobilurin formulationsare more dispersible in water, do not have UV blockers, have enhancedstability (i.e., longer lasting), are rainfast and have improvedmobility in soil. In some embodiments, these new strobilurinformulations have increased curative (systemic) and preventativeperformance, are compatible with other agricultural products(surfactants, leaf wetters, fertilizers, etc), and are stable innon-ideal solution conditions such high salt, extreme pH, hard water,elevated temperatures, etc. These enhancements/improvements in theformulation can also help address the resistance of some fungi by being(1) compatible with a second fungicide, either tank-mixed or pre-mixedin the original formulation and (2) requiring less fungicide in eachapplication. In general, these new strobilurin formulations comprisenanoparticles (optionally in aggregate form) of polymer-associatedstrobilurins along with various formulating agents. Before discussing indetail various embodiments of the chemical and physical characteristicsof these nanoparticles and formulating agents we turn to some generalconsiderations of our strobilurin formulations.

First, we note that for many of the aforementioned applications ofstrobilurins the end user would prefer to receive a dry powder orgranulated product containing the strobilurin. Solid products are notonly less expensive and easier to store and ship, but, generally,handling and environment risks (e.g., spills) are reduced as compared toliquid formulations. The dry product is typically added to water in thespray tank, agitated, and applied to the plant or fungus. It is usefulthat the dry product disperse quickly in the spray tank and that therebe as little as possible or no non-dispersible fraction (which cansediment or cake and can cause problems with spray equipment). Althoughgranulation formulations are common in the art, it is important to notethat individual formulations are not necessarily transferable from oneactive to another. Each active and application may need a differentformulation, which can vary according to the target fungus, the crop towhich it is applied, the geography of its application, applicableregulatory structure, and intensity of infestation among other factors.Formulation development, even with well known actives, is a complex andempirical process.

Second, formulation development (e.g., of granulation formulations)using strobilurins and nanoparticles of polymer-associated activeingredient is non-trivial. In particular, traditional granulationprocesses are not particularly suitable to strobilurins andnanoparticles of polymer-associated active ingredient. For example,traditional granulation of water-insoluble active ingredients normallyinvolves first absorbing the active ingredient to a water-dispersible orwater-soluble carrier, followed by addition of the other granulationingredients and granulating. With our formulations, we do not use atraditional carrier. In addition, active ingredients with low meltingpoints are difficult to granulate because the heat applied or generatedduring extrusion tends to melt the active ingredient and causeseparation during granulation. As shown in Table 3, many strobilurinshave low melting points and can therefore suffer from this problem.Using nanoparticles of polymer-associated strobilurin compounds wasfound to facilitate the granulation of these otherwise difficult togranulate actives ingredients by eliminating the need for lowtemperature granulation equipment (to prevent melting of the active). Itwas also found to facilitate the granulation of semi-solid or evenliquid active ingredients. Surprisingly, during granulation no phaseseparation or apparent melting of these active ingredients occurred. Infact, even if the granules were heated to above the melting point of theactive ingredient no phase separation or apparent melting of the activeingredient occurred. Without wishing to be bound by theory, it isthought that the presence of the polymer nanoparticles provides a stableenvironment for the active ingredients (even when the formulation isbrought to a temperature above the active's melting point), preventingphase separation.

Third, in some embodiments, in order to make a water-dispersiblegranulated formulation with nanoparticles of polymer-associated activeingredient it was necessary to add a dispersant and a wetting agent.Although formulation agents, such as dispersants and wetting agents areknown in the art, the selection of particular compounds and amounts fornanoparticles of polymer-associated active ingredient is non-trivial.Some dispersants, for example, were found to give rise to a negativeeffect in our formulations, e.g., dispersants like Soprophor BSU whichare known to help decrease the particle size in standard granulatedformulations unexpectedly gave rise to larger aggregates in ourformulations. Furthermore, the addition of a salt (e.g., phosphatebuffered saline solution) was necessary in certain cases to maintain thestability of the formulation. This was surprising since normally, theaddition of salt would cause the precipitation of the active ingredient(salting out effect).

Fourth, we have managed to produce high active ingredient (e.g., 20-50weight %) content solid formulations using the nanoparticles ofpolymer-associated active ingredient. This is, in general, quitedifficult to achieve using traditional solid formulating techniques,particularly if the active ingredient has a low melting point or is notsolid at room temperature. Traditionally, in order to have such highactive content formulations that have acceptable qualities such as rapiddispersion in water, adequate stability when dispersed, long-termstorage stability, etc., a suspension concentrate is needed. Suspensionconcentrate formulations, though, have several problems ranging from thehydrolysis of the active ingredient, lower shelf life, and temperaturesensitivity. Some active ingredients cannot be produced as suspensionconcentrates, because of the low melting point of the active ingredient.Low-melting active ingredients tend to be less stable over long termstorage. Additionally, active ingredients with moderate or high watersolubility are difficult to formulate as suspension concentrates becausethey have a tendency to recrystallize and increase in particle size overtime, causing stability problems. Solid formulations do not suffer fromhydrolysis issues because the formulation is nearly devoid of water. Asshown in the Examples, our solid formulations are stable to temperaturecycling and do not show any recrystallization or phase separation of theactive ingredient even after repeated temperature cycling. In light ofthese results our solid formulations are expected to have a long shelflife.

Fifth, as an alternative to the aforementioned solid formulations wehave also prepared high-concentration liquid suspensions (HSLS). Thesehigh-concentration liquid suspensions contain a significant amount ofactive ingredient associated with polymer nanoparticles and are added towater in a spray tank, agitated, and applied to the plant or fungus.These formulations look like the traditional suspension concentratesthat are discussed above and available from many manufacturers. However,because the nanoparticles of polymer-associated active ingredient, theformulations are prepared in different ways, described below, ascompared to the traditional methods. Traditional suspension concentratesare milled surfactant-stabilized formulations of hard solid crystallineparticles. In our case, because the polymer is a compressible,solvent-swellable solid, traditional methods would not work. Instead, wetypically first manufacture the polymer nanoparticles, load them withactive ingredient, and form the high-concentration liquid suspensioneither by drying the loaded polymer nanoparticles (with formulationagents if necessary) and re-suspending at the desired concentration.Alternatively, high concentration liquid suspensions with our polymernanoparticles can be made by using water as the solvent during theloading process and removing water until the loaded polymernanoparticles are at the desired concentration. Traditional suspensionconcentrates also require an anti-settling agent or thickener such asxanthan gum. The gum provides a polymer network that helps stabilize themicron-sized particles of active ingredient and prevent settling andcoalescence. In our formulations, this is not required, because ourparticle size is smaller (nano vs. micro size) and hence settling andcoalescence is less of a problem. In addition, without wishing to belimited by any theory, it is thought that the polymer nanoparticlesthemselves can help stabilize the formulation when dispersed at highconcentration in water.

Sixth, because our formulations are based around nanoparticles ofpolymer-associated active ingredients, we can help improve the skinsensitization or irritation issue for some strobilurins as mentionedabove. Indeed, we have found that if skin exposure occurs they can berinsed off more effectively than with traditional formulations such asEC formulations.

Seventh, because our formulations are based around nanoparticles ofpolymer-associated active ingredients, they are stable to relativelyhigh salt conditions. Stability in high salt conditions is requiredespecially when the formulation is to be mixed with other secondaryagricultural products such as a concentrated fertilizer mix, exposed tohigh salt conditions (e.g., used in or with hard waters) mixed withother formulations (other pesticides, fungicides, and herbicides) ormixed with other tank-mix adjuvants. The ability to mix our formulationswith other products can be beneficial to the end user becausesimultaneous agricultural products can be applied in a singleapplication.

Eighth, our formulations are rainfast. Without wishing to be bound bytheory, polymer-associated active ingredients have an enhanced affinityto the target areas of the plant (and fungus). When the formulation isapplied to a plant/fungus and then exposed to rain, the enhancedaffinity can prevent washing off due to rain.

Formulations—Components

In various aspects, the present disclosure provides formulations thatcomprise nanoparticles (optionally in aggregate form) ofpolymer-associated active ingredient along with various formulatingagents.

Active Ingredient

As used herein, the term “active ingredient” (“ai”, “AI”) refers tostrobilurin compounds (i.e., strobilurins). Strobilurins are naturalsubstances isolated mainly from mushrooms of the genera Strobilurus.Structurally, the basic common feature in this family is the presence of(E)-β-methoxyacrylate group. Many strobilurins have the followinggeneral structure:

where R, n, Y1 and Y2 all vary depending on the strobilurin (see Balba,H. J Envi. Sci. Heath. Part B. 2007, 42, 441.) Some syntheticstrobilurin analogs feature the replacement of the (E)-ß-methoxyacrylategroup with a methoxyiminoacetate group as shown below:

Where X is typically n aromatic ring with varying substituents (seeBalba, H. J Envi. Sci. Heath. Part B. 2007, 42, 441).

Azoxystrobin has the following structure:

Non-limiting examples of strobilurin compounds are: fluoxastrobin,(E)-{2-[6-(2-chlorophenoxy)-5-fluoropyrimidin-4-yloxy]phenyl}(5,6-dihydro-1,4,2-dioxazin-3-yl)methanoneO-methyloxime; fenamidone,(S)-1-anilino-4-methyl-2-methylthio-4-phenylimidazolin-5-one;azoxystrobin, methyl(E)-2-{2-[6-(2-cyanophenoxy)pyrimidin-4-yloxy]phenyl}-3-methoxyacrylate;picoxystrobin, methyl(E)-3-methoxy-2-[2-(6-trifluoromethyl-2-pyridyloxymethyl)phenyl]acrylate;enestrobin, methyl2-{2-[3-(4-chlorophenyl)-1-methylallylideneaminooxymethyl]phenyl}-3-methoxyacrylate;pyraclostrobin, methylN-{2-[1-(4-chlorophenyl)pyrazol-3-yloxymethyl]phenyl}(N-methoxy)carbamate;famoxadone,3-anilino-5-methyl-5-(4-phenoxyphenyl)-1,3-oxazolidine-2,4-dione;dimoxystrobin,(E)-2-(methoxyimino)-N-methyl-2-[α-(2,5-xylyloxy)-o-tolyl]acetamide;metominostrobin,(E)-2-methoxyimino-N-methyl-2-(2-phenoxyphenyl)acetamide; orysastrobin,2[(E)-methoxyimino]-2-[(3E,6E)-2-{5-[(E)-methoxyimino]-4,6-dimethyl-2,8-dioxa-3,7-diazanona-3,6-dienyl}phenyl]-N-methylacetamide;kresoxim-methyl, methyl(E)-methoxyimino[2-(o-tolyloxymethyl)phenyl]acetate; trifloxystrobin,and methyl(E)-methoxyimino-{(E)-α-[1-(α,α,α-trifluoro-m-tolyl)ethylideneaminooxy]-o-tolyl}acetate.

Nanoparticles of Polymer-Associated Active Ingredient

As used herein, the terms “nanoparticles of polymer-associated activeingredient”, “nanoparticles of polymer-associated strobilurin compound”or “active ingredient associated with polymer nanoparticles” refer tonanoparticles comprising one or more collapsed polymers that areassociated with the active ingredient. In some embodiments the collapsedpolymers are cross-linked. As discussed below, in some embodiments, ourformulations may include aggregates of nanoparticles. Exemplary polymersand methods of preparing nanoparticles of polymer-associated activeingredient are described more fully below.

In some embodiments, the active ingredient is associated with preformedpolymer nanoparticles. The associating step may involve dispersing thepolymer nanoparticles in a first solvent and then dispersing the activeingredient in a second solvent that is miscible or partially misciblewith the first solvent, mixing the two dispersions and then eitherremoving the second or first solvent from the final mixture. In someembodiments, all the solvent is removed by vacuum evaporation, freezedrying or spray drying. The associating step may also involve dispersingboth the preformed polymer nanoparticles and active ingredients in acommon solvent and removing all or a portion of the common solvent fromthe final mixture.

In some embodiments, the associating step may involve milling the activeingredient in the presence of pre-formed polymer nanoparticles. It issurprising that if the active ingredient alone is milled under theseconditions; the resulting particle size is significantly larger than ifit is milled in the presence of pre-formed polymer nanoparticles. Ingeneral, size reduction processes such as milling do not enable theproduction of particle sizes that are produced via milling in thepresence of nanoparticles of the current disclosure. Without wishing tobe bound by any theory, it is thought that interaction between theactive ingredient and the nanoparticles during the milling processfacilitates the production of smaller particles than would be formed viamilling in the absence of the nanoparticles.

Non-limiting examples of milling methods that may be used for theassociation step can be found in U.S. Pat. No. 6,604,698 and includeball milling, bead milling, jet milling, media milling, andhomogenization, as well as other milling methods known to those of skillin the art. Non-limiting examples of mills that can be for theassociation step include attritor mills, ball mills, colloid mills, highpressure homogenizers, horizontal mills, jet mills, swinging mills, andvibratory mills. In some embodiments, the associating step may involvemilling the active ingredient in the presence of pre-formed polymernanoparticles and an aqueous phase. In some embodiments, the associatingstep may involve wet or dry milling of the active ingredient in thepresence of pre-formed nanoparticles. In some embodiments, theassociation step may involve milling the active ingredient andpre-formed polymer nanoparticles in the presence of one or moreformulating agents.

In general and without limitation, the active ingredient may beassociated with regions of the polymer nanoparticle that elicit achemical or physical interaction with the active ingredient. Chemicalinteractions can include hydrophobic interactions, affinity pairinteractions, H-bonding, and van der Waals forces. Physical interactionscan include entanglement in polymer chains and/or inclusion within thepolymer nanoparticle structure. In some embodiments, the activeingredient can be associated in the interior of the polymernanoparticle, on the surface of the polymer nanoparticle, or both thesurface and the interior of the polymer nanoparticle. Furthermore, thetype of association interactions between the active ingredient and thepolymer nanoparticle can be probed using spectroscopic techniques suchas NMR, IR, UV-vis, and emission spectroscopies. For example, in caseswhere the strobilurin active ingredient is normally crystalline when notassociated with the polymer nanoparticles, the nanoparticles ofpolymer-associated strobilurin compounds typically do not show theendothermic melting peak or show a reduced endothermic melting peak ofthe pure crystalline active ingredient as seen in differential thermalanalysis (DTA) or differential scanning calorimetry (DSC) measurements(see, e.g., FIG. 1 which is discussed in the Examples).

Nanoparticles of polymer-associated active ingredients can be preparedwith a range of average diameters, e.g., between about 1 nm and about500 nm. The size of the nanoparticles can be adjusted in part by varyingthe size and number of polymers that are included in the nanoparticles.In some embodiments, the average diameter ranges from about 1 nm toabout 10 nm, from about 1 nm to about 20 nm, from about 1 nm to about 30nm, from about 1 nm to about 50 nm, from about 10 nm to about 50 nm,from about 10 nm to about 100 nm, from about 20 nm to about 100 nm, fromabout 20 nm to about 100 nm, from about 50 nm to about 200 nm, fromabout 50 nm to about 250 nm, from about 50 nm to about 300 nm, fromabout 100 nm to about 250 nm, from about 100 nm to about 300 nm, fromabout 200 nm to about 300 nm, from about 200 nm to about 500 nm, fromabout 250 nm to about 500 nm, and from about 300 nm to about 500 nm.These and other average diameters described herein are based on volumeaverage particle sizes that were measured in solution by dynamic lightscattering on a Malvern Zetasizer ZS in CIPAC D water, 0.1M NaCl, or indeionized water at 200 ppm active concentration. Various forms ofmicroscopies can also be used to visualize the sizes of thenanoparticles such as atomic force microscopy (AFM), transmissionelectron microscopy (TEM), scanning electron microscopy (SEM) andoptical microscopy.

In some embodiments, the aggregates have an average particle sizebetween about 10 nm and about 5,000 nm when dispersed in water undersuitable conditions. In some embodiments, the aggregates have an averageparticle size between about 10 nm and about 1,000 nm. In someembodiments, the aggregates have an average particle size between about10 nm and about 500 nm. In some embodiments, the aggregates have anaverage particle size between about 10 nm and about 300 nm. In someembodiments, the aggregates have an average particle size between about10 nm and about 200 nm. In some embodiments, the aggregates have anaverage particle size between about 50 nm and about 5,000 nm. In someembodiments, the aggregates have an average particle size between about50 nm and about 1,000 nm. In some embodiments, the aggregates have anaverage particle size between about 50 nm and about 500 nm. In someembodiments, the aggregates have an average particle size between about50 nm and about 300 nm. In some embodiments, the aggregates have anaverage particle size between about 50 nm and about 200 nm. In someembodiments, the aggregates have an average particle size between about100 nm and about 5,000 nm. In some embodiments, the aggregates have anaverage particle size between about 100 nm and about 1,000 nm. In someembodiments, the aggregates have an average particle size between about100 nm and about 500 nm. In some embodiments, the aggregates have anaverage particle size between about 100 nm and about 300 nm. In someembodiments, the aggregates have an average particle size between about100 nm and about 200 nm. In some embodiments, the aggregates have anaverage particle size between about 500 nm and about 5000 nm. In someembodiments, the aggregates have an average particle size between about500 nm and about 1000 nm. In some embodiments, the aggregates have anaverage particle size between about 1000 nm and about 5000 nm. Particlesize can be measured by the techniques described above.

As described in detail in the examples, in some embodiments, pre-formedpolymer nanoparticles that have been associated with active ingredientto generate nanoparticles or aggregates of nanoparticles ofpolymer-associated active ingredients (associated nanoparticles) can berecovered after extraction of the active ingredient. In someembodiments, the active ingredient can be extracted from nanoparticlesor aggregates of nanoparticles of polymer-associated active ingredientby dispersing the associated nanoparticles in a solvent that dissolvesthe active ingredient but that is known to disperse the un-associated,preformed nanoparticles poorly or not at all. In some embodiments, afterextraction and separation, the insoluble nanoparticles that arerecovered have a size that is smaller than the nanoparticles oraggregates of nanoparticles of polymer-associated active ingredients asmeasured by DLS. In some embodiments, after extraction and separation,the insoluble nanoparticles that are recovered have a size that issimilar or substantially the same as the size of original pre-formedpolymer nanoparticles (prior to association) as measured by DLS. In someembodiments, the nanoparticles are prepared from poly(methacrylicacid-co-ethyl acrylate). In some embodiments, the active ingredient isazoxystrobin. In some embodiments, the extraction solvent isacetonitrile.

It should be understood that the association step to generatenanoparticles of polymer associated active ingredient need notnecessarily lead to association of the entire fraction the activeingredient in the sample with pre-formed polymer nanoparticles (not allmolecules of the active ingredient in the sample must be associated withpolymer nanoparticles after the association step). Likewise, theassociation step need not necessarily lead to the association of theentire fraction of the pre-formed nanoparticles in the sample withactive ingredient (not all nanoparticle molecules in the sample must beassociated with the active ingredient after the association step).

Similarly, in formulations comprising nanoparticles ofpolymer-associated active, the entire fraction of active ingredient inthe formulation need not associated with pre-formed polymernanoparticles (not all molecules of the active ingredient in the samplemust be associated with polymer nanoparticles in the formulation).Likewise, in formulations comprising nanoparticles of polymer-associatedactive ingredient, the entire fraction of pre-formed polymernanoparticles in the formulation need not be associated with activeingredient (not all of nanoparticle molecules in the sample must beassociated with the active ingredient in the formulation).

In some embodiments, the nanoparticles are prepared using a polymer thatis a polyelectrolyte. Polyelectrolytes are polymers that contain monomerunits of ionized or ionizable functional groups, they can be linear,branched, hyperbranched or dendrimeric, and they can be synthetic ornaturally occurring. Ionizable functional groups are functional groupsthat can be rendered charged by adjusting solution conditions, whileionized functional group refers to chemical functional groups that arecharged regardless of solution conditions. The ionized or ionizablefunctional group can be cationic or anionic, and can be continuous alongthe entire polymer chain (e.g., in a homopolymer), or can have differentfunctional groups dispersed along the polymer chain, as in the case of aco-polymer (e.g., a random co-polymer). In some embodiments, the polymercan be made up of monomer units that contain functional groups that areeither anionic, cationic, both anionic and cationic, and can alsoinclude other monomer units that impart a specific desirable property tothe polymer.

In some embodiments, the polyelectrolyte is a homopolymer. Non limitingexamples of homopolymer polyelectrolytes include: poly(acrylic acid),poly(methacrylic acid), poly(styrene sulfonate), poly(ethyleneimine),chitosan, poly(dimethylammonium chloride), poly(allylaminehydrochloride), and carboxymethyl cellulose.

In some embodiments, the polyelectrolyte is a co-polymer. Non limitingexamples of co-polymer polyelectrolytes include: poly(methacrylic acidco-ethyl acrylate); poly(methacrylic acid-co-styrene); poly(methacrylicacid-co-butylmethacrylate); poly[acrylic acid-co-poly(ethylene glycol)methyl ether methacrylate]; or poly(n-butylmethacrylcate-co-methacrylicacid).

In some embodiments, the polyelectrolyte can be made from one or moremonomer units to form homopolymers, copolymers or graft copolymers of:ethylene; ethylene glycol; ethylene oxide; carboxylic acids includingacrylic acid, methacrylic acid, itaconic acid, and maleic acid;polyoxyethylenes or polyethyleneoxide; and unsaturated ethylenic mono ordicarboxylic acids; lactic acids; amino acids; amines includingdimethlyammonium chloride, allylamine hydrochloride; methacrylic acid;ethyleneimine; acrylates including methyl acrylate, ethyl acrylate,propyl acrylate, n-butyl acrylate (“BA”), isobutyl acrylate, 2-ethylacrylate, and t-butyl acrylate; methacrylates including ethylmethacrylate, n-butyl methacrylate, and isobutyl methacrylate;acrylonitriles; methacrylonitrile; vinyls including vinyl acetate,vinylversatate, vinylpropionate, vinylformamide, vinylacetamide,vinylpyridines, and vinyllimidazole; vinylnapthalene, vinylnaphthalenesulfonate, vinylpyrrolidone, vinyl alcohol; aminoalkyls includingaminoalkylacrylates, aminoalkylsmethacrylates, andaminoalkyl(meth)acrylamides; styrenes including styrene sulfonate;d-glucosamine; glucaronic acid-N-acetylglucosamine;N-isopropylacrylamide; vinyl amine. In some embodiments, thepolyelectrolyte polymer can include groups derived from polysaccharidessuch as dextran, gums, cellulose, or carboxymethyl cellulose.

In some embodiments, the polyelectrolyte comprises poly(methacrylicacid-co-ethyl acrylate) polymer. In some embodiments, the mass ratio ofmethacrylic acid to ethyl acrylate in the poly(methacrylic acid-co-ethylacrylate) polymer is between about 50:50 and about 95:5. In someembodiments, the mass ratio of methacrylic acid to ethyl acrylate in thepoly(methacrylic acid-co-ethyl acrylate) polymer is between about 70:30and about 95:5. In some embodiments, the mass ratio of methacrylic acidto ethyl acrylate in the poly(methacrylic acid-co-ethyl acrylate)polymer is between about 80:20 and about 95:5. In some embodiments, themass ratio of methacrylic acid to ethyl acrylate in the poly(methacrylicacid-co-ethyl acrylate) polymer is between about 85:15 and about 95:5.

In some embodiments, the polyelectrolyte comprises poly(methacrylicacid-co-styrene) polymer. In some embodiments, the mass ratio ofmethacrylic acid to styrene in the poly(methacrylic acid-co-styrene)polymer is between about 50:50 and about 95:5. In some embodiments, themass ratio of methacrylic acid to styrene in the poly(methacrylicacid-co-styrene) polymer is between about 70:30 and about 95:5. In someembodiments, the mass ratio of methacrylic acid to styrene in thepoly(methacrylic acid-co-styrene) polymer is between about 80:20 andabout 95:5. In some embodiments, the mass ratio of methacrylic acid tostyrene in the poly(methacrylic acid-co-styrene) polymer is betweenabout 85:15 and about 95:5.

In some embodiments, the mass ratio of methacrylic acid to butylmethacrylate in the poly(methacrylic acid-co-butylmethacrylate) polymeris between about 50:50 and about 95:5. In some embodiments, the massratio of methacrylic acid to butyl methacrylate in the poly(methacrylicacid-co-butylmethacrylate) polymer is between about 70:30 and about95:5. In some embodiments, the mass ratio of methacrylic acid to butylmethacrylate in the poly(methacrylic acid-co-butylmethacrylate) polymeris between about 80:20 and about 95:5. In some embodiments, the massratio of methacrylic acid to butyl methacrylate in the poly(methacrylicacid-co-butylmethacrylate) polymer is between about 85:15 and about95:5.

In some embodiments, the homo or co-polymer is water soluble at pH 7. Insome embodiments, the polymer has solubility in water above about 1weight %. In some embodiments, the polymer has solubility in water aboveabout 2 weight %. In some embodiments, the polymer has solubility inwater above about 3 weight %. In some embodiments, the polymer hassolubility in water above about 4 weight %. In some embodiments, thepolymer has solubility in water above about 5 weight %. In someembodiments, the polymer has solubility in water above about 10 weight%. In some embodiments, the polymer has solubility in water above about20 weight %. In some embodiments, the polymer has solubility in waterabove about 30 weight %. In some embodiments, the polymer has solubilityin water between about 1 and about 30 weight %. In some embodiments, thepolymer has solubility in water between about 1 and about 10 weight %.In some embodiments, the polymer has solubility in water between about 5and about 10 weight %. In some embodiments, the polymer has solubilityin water between about 10 and about 30 weight %. In some embodiments thesolubility of the polymer in water can also be adjusted by adjusting pHor other solution conditions in water.

In some embodiments, the polyelectrolyte polymer has a weight average(M_(w)) molecular weight between about 100,000 and about 4,000,000Daltons. In some embodiments, the polyelectrolyte polymer has a weightaverage molecular weight between about 100,000 and about 2,000,000Daltons. In some embodiments, the polyelectrolyte polymer has a weightaverage molecular weight between about 100,000 and about 1,000,000Daltons. In some embodiments, the polyelectrolyte polymer has a weightaverage molecular weight between about 100,000 and about 750,000Daltons. In some embodiments, the polyelectrolyte polymer has a weightaverage molecular weight between about 100,000 and about 500,000Daltons. In some embodiments, the polyelectrolyte polymer has a weightaverage molecular weight between about 100,000 and about 200,000Daltons. In some embodiments, the polyelectrolyte polymer has a weightaverage molecular weight between about 200,000 and about 2,000,000Daltons. In some embodiments, the polyelectrolyte polymer has a weightaverage molecular weight between about 200,000 and about 1,000,000Daltons. In some embodiments, the polyelectrolyte polymer has a weightaverage molecular weight between about 200,000 and about 500,000Daltons. In some embodiments, the polyelectrolyte polymer has a weightaverage molecular weight between about 300,000 and about 2,000,000Daltons. In some embodiments, the polyelectrolyte polymer has a weightaverage molecular weight between about 300,000 and about 1,000,000Daltons. In some embodiments, the polyelectrolyte polymer has a weightaverage molecular weight between about 300,000 and about 500,000Daltons.

In some embodiments, the apparent molecular weight of thepolyelectrolyte polymer (e.g., the molecular weight determined viacertain analytical measurements such as size exclusion chromatography orDLS) is lower than the actual molecular weight of a polymer due tocrosslinking within the polymer. In some embodiments, a crosslinkedpolyelectrolyte polymer of the present disclosure might have a higheractual molecular weight than the experimentally determined apparentmolecular weight. In some embodiments, a crosslinked polyelectrolytepolymer of the present disclosure might be a high molecular weightpolymer despite having a low apparent molecular weight.

Nanoparticles of polymer-associated active ingredients and/or aggregatesof these nanoparticles can be part of a formulation in differentamounts. The final amount will depend on many factors including the typeof formulation (e.g., liquid or solid, granule or powder, concentratedor not, etc.). In some instances the nanoparticles (including both thepolymer and active ingredient components) make up between about 1 andabout 98 weight % of the total formulation. In some embodiments, thenanoparticles make up between about 1 and about 90 weight % of the totalformulation. In some embodiments, the nanoparticles make up betweenabout 1 and about 75 weight % of the total formulation. In someembodiments, the nanoparticles make up between about 1 and about 50weight % of the total formulation. In some embodiments, thenanoparticles make up between about 1 and about 30 weight % of the totalformulation. In some embodiments, the nanoparticles make up betweenabout 1 and about 25 weight % of the total formulation. In someembodiments, the nanoparticles make up between about 1 and about 10weight % of the total formulation. In some embodiments, thenanoparticles make up between about 10 and about 25 weight % of thetotal formulation. In some embodiments, the nanoparticles make upbetween about 10 and about 30 weight % of the total formulation. In someembodiments, the nanoparticles make up between about 10 and about 50weight % of the total formulation. In some embodiments, thenanoparticles make up between about 10 and about 75 weight % of thetotal formulation. In some embodiments, the nanoparticles make upbetween about 10 and about 90 weight % of the total formulation. In someembodiments, the nanoparticles make up between about 10 and about 98weight % of the total formulation. In some embodiments, thenanoparticles make up between about 25 and about 50 weight % of thetotal formulation. In some embodiments, the nanoparticles make upbetween about 25 and about 75 weight % of the total formulation. In someembodiments, the nanoparticles make up between about 25 and about 90weight % of the total formulation. In some embodiments, thenanoparticles make up between about 30 and about 98 weight % of thetotal formulation. In some embodiments, the nanoparticles make upbetween about 50 and about 90 weight % of the total formulation. In someembodiments, the nanoparticles make up between about 50 and about 98weight % of the total formulation. In some embodiments, thenanoparticles make up between about 75 and about 90 weight % of thetotal formulation. In some embodiments, the nanoparticles make upbetween about 75 and about 98 weight % of the total formulation.

In some embodiments, the nanoparticles of polymer-associated activeingredients are prepared according to a method disclosed in UnitedStates Patent Application Publication No. 20100210465, the entirecontents of which are incorporated herein by reference. In someembodiments, polymer nanoparticles without active ingredients are madeby collapse of a polyelectrolyte with a collapsing agent and thenrendering the collapsed conformation permanent by intra-particlecross-linking. The active ingredient is then associated with thispre-formed polymer nanoparticle. In some embodiments, the formulationcontains the same amount (by weight) of active ingredient and polymer,while in other embodiments the ratio of active ingredient to polymer (byweight) can be between about 1:10 and about 10:1, between about 1:10 andabout 1:5, between about 1:5 and about 1:4, between about 1:4 and about1:3, between about 1:3 and about 1:2, between about 1:2 and about 1:1,between about 1:5 and about 1:1, between about 5:1 and about 1:1,between about 2:1 and about 1:1, between about 3:1 and about 2:1,between about 4:1 and about 3:1, between about 5:1 and about 4:1,between about 10:1 and about 5:1, between about 1:3 and about 3:1,between about 5:1 and about 1:1, between about 1:5 and about 5:1, orbetween about 1:2 and about 2:1.

As noted above, in some embodiments, the associating step may involvedispersing the polymer nanoparticles in a first solvent, dispersing theactive ingredient in a second solvent that is miscible or partiallymiscible with the first solvent, mixing the two dispersions and theneither removing the second or first solvent from the final mixture.

Alternatively, in some embodiments, the associating step may involvedispersing both the pre-formed polymer nanoparticles and activeingredient in a common solvent and removing all or a portion of thecommon solvent from the final mixture. The final form of thenanoparticles of polymer-associated active ingredient can be either adispersion in a common solvent or a dried solid. The common solvent istypically one that is capable of swelling the polymer nanoparticles aswell as dissolving the active ingredient at a concentration of at leastabout 10 mg/mL, e.g., at least about 20 mg/mL. The polymer nanoparticlesare typically dispersed in the common solvent at a concentration of atleast about 10 mg/mL, e.g., at least about 20 mg/mL. In someembodiments, the common solvent is an alcohol (either long or shortchain), preferably methanol or ethanol. In some embodiments the commonsolvent is selected from alkenes, alkanes, alkynes, phenols,hydrocarbons, chlorinated hydrocarbons, ketones, and ethers. In someembodiments, the common solvent is a mixture of two or more differentsolvents that are miscible or partially miscible with each other. Someor all of the common solvent is removed from the dispersion ofpre-formed polymer nanoparticles and active ingredients by either directevaporation or evaporation under reduced pressure. The dispersion can bedried by a range of processes known by a practitioner of the art such aslyophilization (freeze-drying), spray-drying, tray-drying, evaporation,jet drying, or other methods to obtain the nanoparticles ofpolymers-associated with active ingredients. In general, the amount ofsolvent that is removed from the dispersion described above will dependon the final type of formulation that is desired. This is illustratedfurther in the Examples and in the general description of specificformulations.

In some instances the solids content (including both the polymer andactive ingredient components as well as other solid form formulatingagents) of the formulation is between about 1 and about 98 weight % ofthe total formulation. In some embodiments, the solids content of theformulation is between about 1 and about 90 weight % of the totalformulation. In some embodiments, the solids content of the formulationis between about 1 and about 75 weight % of the total formulation. Insome embodiments, the solids content of the formulation is between about1 and about 50 weight % of the total formulation. In some embodiments,the solids content of the formulation is between about 1 and about 30weight % of the total formulation. In some embodiments, the solidscontent of the formulation is between about 1 and about 25 weight % ofthe total formulation. In some embodiments, the solids content of theformulation is between about 1 and about 10 weight % of the totalformulation. In some embodiments, the solids content of the formulationis between about 10 and about 25 weight % of the total formulation. Insome embodiments, the solids content of the formulation is between about10 and about 30 weight % of the total formulation. In some embodiments,the solids content of the formulation is between about 10 and about 50weight % of the total formulation. In some embodiments, the solidscontent of the formulation is between about 10 and about 75 weight % ofthe total formulation. In some embodiments, the solids content of theformulation is between about 10 and about 90 weight % of the totalformulation. In some embodiments, the solids content of the formulationis between about 10 and about 98 weight % of the total formulation. Insome embodiments, the solids content of the formulation is between about25 and about 50 weight % of the total formulation. In some embodiments,the solids content of the formulation is between about 25 and about 75weight % of the total formulation. In some embodiments, the solidscontent of the formulation is between about 25 and about 90 weight % ofthe total formulation. In some embodiments, the solids content of theformulation is between about 30 and about 98 weight % of the totalformulation. In some embodiments, the solids content of the formulationis between about 50 and about 90 weight % of the total formulation. Insome embodiments, the solids content of the formulation is between about50 and about 98 weight % of the total formulation. In some embodiments,the solids content of the formulation is between about 75 and about 90weight % of the total formulation. In some embodiments, the solidscontent of the formulation is between about 75 and about 98 weight % ofthe total formulation.

Formulating Agents

As used herein, the term “formulating agent” refers to any othermaterial used in the formulation other than the nanoparticles ofpolymer-associated active ingredient. Formulating agents can include,but are not limited to, compounds that can act as a dispersants orwetting agents, inert fillers, solvents, surfactants, anti-freezingagents, anti-settling agents or thickeners, disintegrants, andpreservatives.

In some embodiments, a formulation may include a dispersant or wettingagent or both. In some embodiments the same compound may act as both adispersant and a wetting agent. A dispersant is a compound that helpsthe nanoparticles (or aggregates of nanoparticles) disperse in water.Without wishing to be bound by any theory, dispersants are thought toachieve this result by absorbing on to the surface of the nanoparticlesand thereby limiting re-aggregation. Wetting agents increase thespreading or penetration power of a liquid when placed onto thesubstrate (e.g., leaf). Without wishing to be bound by any theory,wetting agents are thought to achieve this result by reducing theinterfacial tension between the liquid and the substrate surface.

In a similar manner, some formulating agents may demonstrate multiplefunctionality. The categories and listings of specific agents below arenot mutually exclusive. For example, fumed silica, described below inthe thickener/anti-settling agent and anti-caking agent sections, istypically used for these functions. In some embodiments, however, fumedsilica demonstrates the functionality of a wetting agent and/ordispersant. Specific formulating agents listed below are categorizedbased on their primary functionality, however, it is to be understoodthat particular formulating agents may exhibit multiple functions.Certain formulation ingredients display multiple functionalities andsynergies with other formulating agents and may demonstrate superiorproperties in a particular formulation but not in another formulation.

In some embodiments, a dispersant or wetting agent is selected fromorganosilicones (e.g., SYLGARD 309 from Dow Corning Corporation orSILWET L77 from Union Carbide Corporation) including polyalkylene oxidemodified polydimethylsiloxane (SILWET L7607 from Union CarbideCorporation), methylated seed oil, and ethylated seed oil (e.g., SCOILfrom Agsco or HASTEN from Wilfarm), alkylpolyoxyethylene ethers (e.g.,ACTIVATOR 90), alkylarylalolates (e.g., APSA 20), alkylphenol ethoxylateand alcohol alkoxylate surfactants (e.g., products sold by Huntsman),fatty acid, fatty ester and fatty amine ethoxylates (e.g., products soldby Huntsman), products sold by Cognis such as sorbitan and ethoxylatedsorbitan esters, ethoxylated vegetable oils, alkyl, glycol and glycerolesters and glycol ethers, tristyrylphenol ethoxylates, anionicsurfactants such as sulfonates, such as sulfosuccinates, alkylarylsulphonates, alkyl napthalene sulfonates (e.g., products sold byAdjuvants Unlimited), calcium alkyl benzene sulphonates, and phosphateesters (e.g., products sold by Huntsman Chemical or BASF), as salts ofsodium, potassium, ammonium, magnesium, triethanolamine (TEA), etc.

Other specific examples of the above sulfates include ammonium laurylsulfate, magnesium lauryl sulfate, sodium 2-ethyl-hexyl sulfate, sodiumactyl sulfate, sodium oleyl sulfate, sodium tridecyl sulfate,triethanolamine lauryl sulfate, ammonium linear alcohol, ether sulfateammonium nonylphenol ether sulfate, and ammonium monoxynol-4-sulfate.Other examples of dispersants and wetting agents include, sulfosuccinamates, disodium N-octadecylsulfo-succinamate; tetrasodiumN-(1,2-dicarboxyethyl)-N-octadecylsulfo-succinamate; diamyl ester ofsodium sulfosuccinic acid; dihexyl ester of sodium sulfosuccinic acid;and dioctyl esters of sodium sulfosuccinic acid; dihexyl ester of sodiumsulfosuccinic acid; and dioctyl esters of sodium sulfosuccinic acid;castor oil and fatty amine ethoxylates, including sodium, potassium,magnesium or ammonium salts thereof. Dispersants and wetting agents alsoinclude natural emulsifiers, such as lecithin, fatty acids (includingsodium, potassium or ammonium salts thereof) and ethanolamides andglycerides of fatty acids, such as coconut diethanolamide and coconutmono- and diglycerides. Dispersants and wetting agents also includesodium polycarboxylate (commercially available as Geropon TA/72); sodiumsalt of naphthalene sulfonate condensate (commercially available asMorwet (D425, D809, D390, EFW); calcium naphthalene sulfonates(commercially available as DAXAD 19LCAD); sodium lignosulfonates andmodified sodium lignosulfonates; aliphatic alcohol ethoxylates;ethoxylated tridecyl alcohols (commercially available as Rhodasurf(BC420, BC610, BC720, BC 840); Ethoxylated tristeryl phenols(commercially available as Soprophor BSU); sodium methyl oleyl taurate(commercially available as Geropon T77); tristyrylphenol ethoxylates andesters; ethylene oxide-propylene oxide block copolymers; non-ionic blockcopolymers (commercially available as Atlox (4912). Examples ofdispersants and wetting agents include, but are not limited to, sodiumdodecylbenzene sulfonate; N-oleyl N-methyl taurate;1,4-dioctoxy-1,4-dioxo-butane-2-sulfonic acid; sodium lauryl sulphate;sodium dioctyl sulphosuccinate; aliphatic alcohol ethoxylates;nonylphenol ethoxylates. Dispersants and wetting agents also includesodium taurates; and sodium or ammonium salts of maleic anhydridecopolymers, lignosulfonic acid formulations or condensed sulfonatesodium, potassium, magnesium or ammonium salts, polyvinylpyrrolidone(available commercially as POLYPLASDONE XL-10 from InternationalSpecialty Products or as KOLLIDON C1 M-10 from BASF Corporation),polyvinyl alcohols, modified or unmodified starches, methylcellulose,hydroxyethyl or hydroxypropyl methylcellulose, carboxymethylmethylcellulose, or combinations, such as a mixture of eitherlignosulfonic acid formulations or condensed sulfonate sodium,potassium, magnesium or ammonium salts with polyvinylpyrrolidone (PVP).

In some embodiments, the dispersants and wetting agents can combine tomake up between about 1 and about 30 weight % of the formulation. Forexample, dispersants and wetting agents can make up between about 1 andabout 20 weight %, about 1 and about 10 weight %, between about 1 andabout 5 weight %, between about 1 and about 3 weight %, between about 2and about 30 weight %, between about 2 and about 20 weight %, betweenabout 2 and about 10 weight %, between about 3 and about 30 weight %,between about 3 and about 20 weight %, between about 3 and about 10weight %, between about 3 and about 5 weight %, between about 5 andabout 30 weight %, between about 5 and about 20 weight %, between about5 and about 10 weight % of the formulation. In some embodiments,dispersants or wetting agents can make up between about 0.1 and 1 weight% of the formulation.

In some embodiments, a formulation may include an inert filler. Forexample, an inert filler may be included to produce or promote cohesionin forming a wettable granule formulation. An inert filler may also beincluded to give the formulation a certain active loading, density, orother similar physical properties. Non limiting examples of inertfillers that may be used in a formulation include bentonite clay,carbohydrates, proteins, lipids synthetic polymers, glycolipids,glycoproteins, lipoproteins, lignin, lignin derivatives, andcombinations thereof. In a preferred embodiment the inert filler is alignin derivative and is optionally calcium lignosulfonate. In someembodiments, the inert filler is selected from the group consisting of:monosaccharides, disaccharides, oligosaccharides, polysaccharides andcombinations thereof. Specific carbohydrate inert fillers illustrativelyinclude glucose, mannose, fructose, galactose, sucrose, lactose,maltose, xylose, arabinose, trehalose and mixtures thereof such as cornsyrup; sugar alcohols including: sorbitol, xylitol, ribitol, mannitol,galactitol, fucitol, iditol, inositol, volemitol, isomalt, maltitol,lactitol, polyglycitol; celluloses such as carboxymethylcellulose,ethylcellulose, hydroxyethylcellulose, hydroxy-methylethylcellulose,hydroxyethylpropylcellulose, methyl hydroxyethylcellulose,methylcellulose; starches such as amylose, seagel, starch acetates,starch hydroxyethyl ethers, ionic starches, long-chain alkyl starches,dextrins, amine starches, phosphates starches, and dialdehyde starches;plant starches such as corn starch and potato starch; othercarbohydrates such as pectin, amylopectin, xylan, glycogen, agar,alginic acid, phycocolloids, chitin, gum arabic, guar gum, gum karaya,gum tragacanth and locust bean gum; vegetable oils such as corn,soybean, peanut, canola, olive and cotton seed; complex organicsubstances such as lignin and nitrolignin; derivatives of lignin such aslignosulfonate salts illustratively including calcium lignosulfonate andsodium lignosulfonate and complex carbohydrate-based formulationscontaining organic and inorganic ingredients such as molasses. Suitableprotein inert fillers illustratively include soy extract, zein,protamine, collagen, and casein. Inert fillers operative herein alsoinclude synthetic organic polymers capable of promoting or producingcohesion of particle components and such inert fillers illustrativelyinclude ethylene oxide polymers, polyacrylamides, polyacrylates,polyvinyl pyrrolidone, polyethylene glycol, polyvinyl alcohol,polyvinylmethyl ether, polyvinyl acrylates, polylactic acid, and latex.

In some embodiments, a formulation contains between about 1 and about 90weight % inert filler, e.g., between about 1 and about 80 weight %,between about 1 and about 60 weight %, between about 1 and about 40weight %, between about 1 and about 25 weight %, between about 1 andabout 10 weight %, between about 10 and about 90 weight %, between about10 and about 80 weight %, between about 10 and about 60 weight %,between about 10 and about 40 weight %, between about 10 and about 25weight %, between about 25 and about 90 weight %, between about 25 andabout 80 weight %, between about 25 and about 60 weight %, between about25 and about 40 weight %, between about 40 and about 90 weight %,between about 40 and about 80 weight %, or between about 60 and about 90weight %.

In some embodiments, a formulation may include a solvent or a mixture ofsolvents that can be used to assist in controlling the solubility of theactive ingredient itself, the nanoparticles of polymer-associated activeingredients, or other components of the formulation. For example, thesolvent can be chosen from water, alcohols, alkenes, alkanes, alkynes,phenols, hydrocarbons, chlorinated hydrocarbons, ketones, ethers, andmixtures thereof. In some embodiments, the formulation contains asolvent or a mixture of solvents that makes up about 0.1 to about 90weight % of the formulation. In some embodiments, a formulation containsbetween about 0.1 and about 90 weight % solvent, e.g., between about 1and about 80 weight %, between about 1 and about 60 weight %, betweenabout 1 and about 40 weight %, between about 1 and about 25 weight %,between about 1 and about 10 weight %, between about 10 and about 90weight %, between about 10 and about 80 weight %, between about 10 andabout 60 weight %, between about 10 and about 40 weight %, between about10 and about 25 weight %, between about 25 and about 90 weight %,between about 25 and about 80 weight %, between about 25 and about 60weight %, between about 25 and about 40 weight %, between about 40 andabout 90 weight %, between about 40 and about 80 weight %, between about60 and about 90 weight %, between about 0.1 and about 10 weight %,between about 0.1 and about 5 weight %, between about 0.1 and about 3weight %, between about 0.1 and about 1 weight %, between about 0.5 andabout 20 weight %, 0 between about 0.5 and about 10 weight %, betweenabout 0.5 and about 5 weight %, between about 0.5 and about 3 weight %,between about 0.5 and about 1 weight %, between about 1 and about 20weight %, between about 1 and about 10 weight %, between about 1 andabout 5 weight %, between about 1 and about 3 weight %, between about 5and about 20 weight %, between about 5 and about 10 weight %, betweenabout 10 or about 20 weight %.

In some embodiments, a formulation may include a surfactant. Whenincluded in formulations, surfactants can function as wetting agents,dispersants, emulsifying agents, solublizing agents and bioenhancingagents. Without limitation, particular surfactants may be anionicsurfactants, cationic surfactants, nonionic surfactants, amphotericsurfactants, silicone surfactants (e.g., Silwet L77), andfluorosurfactants. Exemplary anionic surfactants include alkylbenzenesulfonates, alkyl sulfonates and ethoxylates, sulfosuccinates, phosphateesters, taurates, alkylnaphthalene sulfonates and polymerslignosulfonates. Exemplary nonionic surfactants include alkylphenolethoxylates, aliphatic alcohol ethoxylates, aliphatic alkylamineethoxylates, amine alkoxylates, sorbitan esters and their ethoxylates,castor oil ethoxylates, ethylene oxide/propylene oxide copolymers andpolymeric surfactants. In some embodiments, surfactants can make upbetween about 1 about 20 weight % of the formulation, e.g., betweenabout 1-15 weight %, between about 1 and about 10 weight %, betweenabout 1 and about 8 weight %, between about 1 and about 6 weight %,between about 1 and about 4 weight %, between about 3 and about 20weight %, between about 3 and about 15 weight %, between about 3 andabout 10 weight %, between about 3 and about 8 weight %, between about 3and about 6 weight %, between about 5 and about 15 weight %, betweenabout 5 and about 10 weight %, between about 5 and about 8 weight %, orbetween about 10 and about 15 weight %. In some embodiments, asurfactant (e.g., a non-ionic surfactant) may be added to a formulationby the end user, e.g., in a spray tank. Indeed, when a formulation isadded to the spray tank it becomes diluted and, in some embodiments, itmay be advantageous to add additional surfactant in order to maintainthe nanoparticles in dispersed form.

In some embodiments, a formulation may include an anti-settling agent orthickener that can help provide stability to a liquid formulation ormodify the rheology of the formulation. Examples of anti-settling agentsor thickeners include, but are not limited to, guar gum; locust beangum; xanthan gum; carrageenan; alginates; methyl cellulose; sodiumcarboxymethyl cellulose; hydroxyethyl cellulose; modified starches;polysaccharides and other modified polysaccharides; polyvinyl alcohol;glycerol alkyd resins such as Latron B-1956 from Rohm & Haas Co., plantoil based materials (e.g., cocodithalymide) with emulsifiers; polymericterpenes; microcrystalline cellulose; methacrylates;poly(vinylpyrrolidone), syrups, polyethylene oxide, and fumed silica(e.g., Aerosil 380). In some embodiments, anti-settling agents orthickeners can make up between about 0.05 and about 10 weight % of theformulation, e.g., about 0.05 to about 5 weight %, about 0.05 to about 3weight %, about 0.05 to about 1 weight %, about 0.05 to about 0.5 weight%, about 0.05 to about 0.1 weight %, about 0.1 to about 5 weight %,about 0.1 to about 3 weight %, about 0.1 to about 1 weight %, about 0.1to about 0.5 weight %, about 0.5 to about 5 weight %, about 0.5 to about3 weight %, about 0.5 to about 1 weight %, about 1 to about 10 weight %,about 1 to about 5 weight %, or about 1 to about 3 weight %. In someembodiments, it is explicitly contemplated that a formulation of thepresent disclosure does not include a compound whose primary function isto act as an anti-settling or thickener. In some embodiments, compoundsincluded in a formulation may have some anti-settling or thickeningfunctionality, in addition to other, primary functionality, soanti-settling or thickening functionality is not a necessary conditionfor exclusion, however, formulation agents used primarily or exclusivelyas anti-settling agents or thickeners may be expressly omitted from theformulations.

In some embodiments, a formulation may include one or more preservativesthat prevent microbial or fungal degradation of the product duringstorage. Examples of preservatives include but are not limited to,tocopherol, ascorbyl palmitate, propyl gallate, butylated hydroxyanisole(BHA), butylated hydroxytoluene (BHT), propionic acid and its sodiumsalt; sorbic acid and its sodium or potassium salts; benzoic acid andits sodium salt; p-hydroxy benzoic acid sodium salt; methyl p-hydroxybenzoate; 1,2-benzisothiazalin-3-one, and combinations thereof. In someembodiments, preservatives can make up about 0.01 to about 0.2 weight %of the formulation, e.g., between about 0.01 and about 0.1 weight %,between about 0.01 and about 0.05 weight %, between about 0.01 and about0.02 weight %, between about 0.02 and about 0.2 weight %, between about0.02 and about 0.1 weight %, between about 0.02 and about 0.05 weight %,between about 0.05 and about 0.2 weight %, between about 0.05 and about0.1 weight %, or between about 0.1 and about 0.2 weight %.

In some embodiments, a formulation may include anti-freezing agents,anti-foaming agents, and/or anti-caking agents that help stabilize theformulation against freezing during storage, foaming during use, orcaking during storage. Examples of anti-freezing agents include, but arenot limited to, ethylene glycol, propylene glycol, and urea. In certainembodiment a formulation may include between about 0.5 and about 10weight % anti-freezing agents, e.g., between about 0.5 and about 5weight %, between about 0.5 and about 3 weight %, between about 0.5 andabout 2 weight %, between about 0.5 and about 1 weight %, between about1 and about 10 weight %, between about 1 and about 5 weight %, betweenabout 1 and about 3 weight %, between about 1 and about 2 weight %,between about 2 and about 10 weight %, between about 3 and about 10weight %, or between about 5 and about 10 weight %.

Examples of anti-foaming agents include, but are not limited to,silicone based anti-foaming agents (e.g., aqueous emulsions of dimethylpolysiloxane, FG-10 from Dow-Corning®, Trans 10A from Trans-Chemo Inc.),and non-silicone based anti-foaming agents such as octanol, nonanol, andsilica. In some embodiments a formulation may include between about 0.05and about 5 weight % of anti-foaming agents, e.g., between about 0.05and about 0.5 weight %, between about 0.05 and about 1 weight %, betweenabout 0.05 and about 0.2 weight %, between about 0.1 and about 0.2weight %, between about 0.1 and about 0.5 weight %, between about 0.1and about 1 weight %, or between about 0.2 and about 1 weight %.

Examples of anti-caking agents include sodium or ammonium phosphates,sodium carbonate or bicarbonate, sodium acetate, sodium metasilicate,magnesium or zinc sulfates, magnesium hydroxide (all optionally ashydrates), sodium alkylsulfosuccinates, silicious compounds, magnesiumcompounds, C10-C22 fatty acid polyvalent metal salt compounds, and thelike. Illustrative of anti-caking ingredients are attapulgite clay,kieselguhr, silica aerogel, silica xerogel, perlite, talc, vermiculite,sodium aluminosilicate, zirconium oxychloride, starch, sodium orpotassium phthalate, calcium silicate, calcium phosphate, calciumnitride, aluminum nitride, copper oxide, magnesium carbonate, magnesiumsilicate, magnesium nitride, magnesium phosphate, magnesium oxide,magnesium nitrate, magnesium sulfate, magnesium chloride, and themagnesium and aluminum salts of C10-C22 fatty acids such as palmiticacid, stearic acid and oleic acid. Anti-caking agents also includerefined kaolin clay, amorphous precipitated silica dioxide, such as HISIL 233 available from PPG Industries, refined clay, such as HUBERSILavailable from Huber Chemical Company, or fumed silica (e.g., Aerosil380) In some embodiments, a formulation may include between about 0.05and about 10 weight % anti-caking agents, e.g., between about 0.05 to 5weight %, between about 0.05 and about 3 weight %, between about 0.05and about 2 weight %, between about 0.05 and about 1 weight %, betweenabout 0.05 and about 0.5 weight %, between about 0.05 and about 0.1weight %, between about 0.1 and about 5 weight %, between about 0.1 andabout 3 weight %, between about 0.1 and about 2 weight %, between about0.1 and about 1 weight %, between about 0.1 and about 0.5 weight %,between about 0.5 and about 5 weight %, between about 0.5 and about 3weight %, between about 0.5 and about 2 weight %, between about 0.5 andabout 1 weight %, between about 1 to 3 weight %, between about 1 to 10weight %, or between about 1 and about 5 weight %.

In some embodiments, a formulation may include a UV-blocking compoundthat can help protect the active ingredient from degradation due to UVirradiation. Examples of UV-blocking compounds include ingredientscommonly found in sunscreens such as benzophenones, benzotriazoles,homosalates, alkyl cinnamates, salicylates such as octyl salicylate,dibenzoylmethanes, anthranilates, methylbenzylidenes, octyl triazones,2-phenylbenzimidazole-5-sulfonic acid, octocrylene, triazines,cinnamates, cyanoacrylates, dicyano ethylenes, etocrilene, drometrizoletrisiloxane, bisethylhexyloxyphenol methoxyphenol triazine,drometrizole, dioctyl butamido triazone, terephthalylidene dicamphorsulfonic acid and para-aminobenzoates as well as ester derivativesthereof, UV-absorbing metal oxides such as titanium dioxide, zinc oxide,and cerium oxide, and nickel organic compounds such as nickel bis(octylphenol) sulfide, etc. Additional examples of each of these classesof UV-blockers may be found in Kirk-Othmer, Encyclopedia of ChemicalTechnology. In some embodiments, a formulation may include between about0.01 and about 2 weight % UV-blockers, e.g., between about 0.01 andabout 1 weight %, between about 0.01 and about 0.5 weight %, betweenabout 0.01 and about 0.2 weight %, between about 0.01 and about 0.1weight %, between about 0.01 and about 0.05 weight %, between about 0.05weight % and about 1 weight %, between about 0.05 and about 0.5 weight%, between about 0.05 and about 0.2 weight %, between about 0.05 andabout 0.1 weight %, between about 0.1 and about 1 weight %, betweenabout 0.1 and about 0.5 weight %, between about 0.1 and about 0.2 weight%, between about 0.2 and about 1 weight %, between about 0.2 and about0.5 weight %, or between about 0.5 and about 1 weight %. In someembodiments, it is explicitly contemplated that a formulation of thepresent disclosure does not include a compound whose primary function isto act as a UV-blocker. In some embodiments, compounds included in aformulation may have some UV-blocking functionality, in addition toother, primary functionality, so UV-blocking is not a necessarycondition for exclusion, however, formulation agents used primarily orexclusively as UV-blockers may be expressly omitted from theformulations.

In some embodiments, a formulation may include a disintegrant that canhelp a solid formulation break apart when added to water. Examples ofsuitable disintegrants include cross-linked polyvinyl pyrrolidone,modified cellulose gum, pregelatinized starch, cornstarch, modified cornstarch (e.g., STARCH 1500) and sodium carboxymethyl starch (e.g.,EXPLOTAB or PRIMOJEL), microcrystalline cellulose, sodium starchglycolate, sodium carboxymethyl cellulose, carmellose, carmellosecalcium, carmellose sodium, croscarmellose sodium, carmellose calcium,carboxymethylstarch sodium, low-substituted hydroxypropyl cellulose,hydroxypropyl methylcellulose, hydroxypropyl cellulose, soypolysaccharides (e.g., EMCOSOY), alkylcelullose, hydroxyalkylcellulose,alginates (e.g., SATIALGINE), dextrans and poly(alkylene oxide) and aneffervescent couple (e.g., citric or ascorbic acid plus bicarbonate),lactose, anhydrous dibasic calcium phosphate, dibasic calcium phosphate,magnesium aluminometasilicate, synthesized hydrotalcite, silicicanhydride and synthesized aluminum silicate. In some embodimentsdisintegrants can make up between about 1 and about 20 weight % of theformulation, e.g., between about 1 and about 15 weight %, between about1 and about 10 weight %, between about 1 and about 8 weight %, betweenabout 1 and about 6 weight %, between about 1 and about 4 weight %,between about 3 and about 20 weight %, between about 3 and about 15weight %, between about 3 and about 10 weight %, between about 3 andabout 8 weight %, between about 3 and about 6 weight %, between about 5and about 15 weight %, between about 5 and about 10 weight %, betweenabout 5 and about 8 weight %, or between about 10 and about 15 weight %.

Formulations

As described above, the nanoparticles of polymer-associated activeingredient can be formulated into different types of formulations fordifferent applications. For example, the types of formulations caninclude wettable granules, wettable powders, and high solid liquidsuspensions. Furthermore, as discussed above, formulation agents caninclude, but are not limited to dispersants, wetting agents,surfactants, anti-settling agents or thickeners, preservatives,anti-freezing agents, anti-foaming agents, anti-caking agents, inertfillers, and UV-blockers.

In some embodiments, a dispersion of polymer nanoparticles and activeingredient in a common solvent is dried (e.g., spray dried) to form asolid containing nanoparticles (optionally in aggregate form) ofpolymer-associated active ingredients. The spray dried solid can then beused as is or incorporated into a formulation containing otherformulating agents to make a wettable granule (WG), wettable powder(WP), or a high solids liquid suspension (HSLS).

In some embodiments, active ingredient is milled in the presence ofpre-formed polymer nanoparticles to form a solid containingnanoparticles (optionally in aggregate form) of polymer-associatedactive ingredients. The solid can then be used as is or incorporatedinto a formulation containing other formulating agents to make awettable granule (WG), wettable powder (WP), or a high solids liquidsuspension (HSLS). In some embodiments, the milling step may beperformed in the presence of one or more formulating agents. In someembodiments, the milling step may be performed in the presence of anaqueous phase.

Wettable Granules (WG)

In some embodiments, the dried solid can be made into a formulation thatis a wettable granule (WG) by adding other formulating agents and byextruding the formulation to form granules. In some embodiments, a WGformulation may be made by mixing together a dried (e.g., spray-dried,freeze dried, etc.) or milled solid comprising nanoparticles ofpolymer-associated active ingredient (or aggregates thereof), a wettingagent (e.g., a surfactant such as Soprophor 4D 384 or BSU) and/or adispersant (e.g., a lignosulfonate such as Reax 88B, etc.) and an inertfiller (e.g., lactose). In some embodiments a WG can be made using awetting agent (e.g., a surfactant such as Soprophor 4D384 or BSU) and adispersant (e.g., a lignosulfonate such as Reax 88B, etc.).

In some exemplary embodiments, described in more detail in the Examplessection, the components of the WG formulation are all mixed in a vessel,moistened with about 30 to about 50% equivalent mass of water, and theresulting semi-solid is extruded to make granules. In some embodiments,the formulation of the final WG can be (by weight): 0-5% dispersant,0-5% wetting agent, 5-80% nanoparticles of polymer-associated activeingredient (optionally in aggregate form), and inert filler to 100%. Insome embodiments, the formulation of the final WG can be (by weight):0.5-5% dispersant, 0.5%-5% wetting agent, 5-80% nanoparticles ofpolymer-associated active ingredient (optionally in aggregate form), andinert filler to 100%. As described above in the Formulating Agents andNanoparticles of polymer-associated active ingredient sections, a widevariety of formulating agent(s) and various concentrations ofnanoparticles (including aggregates), wetting agents, dispersants,fillers and other formulating agents can be used to prepare exemplaryformulations, e.g. wettable granules.

In some embodiments, a WG formulation comprising nanoparticles ofpolymer-associated active ingredients (optionally in aggregate form) maybe made by using a dispersion of polymer nanoparticles and activeingredient in a common solvent, preferably methanol. In someembodiments, a WG formulation can be made by adding the dispersion incommon solvent into an aqueous solution containing a wetting agent(e.g., a surfactant such as Soprophor 4D 384 or BSU) and/or a dispersant(e.g., a lignosulfonate such as Reax 88B, etc.) and an inert filler(e.g., lactose), drying (freeze drying, spray drying, etc.) theresulting mixture to from a solid and then granulating the solid toobtain a WG formulation comprising nanoparticles of polymer-associatedactive ingredients (optionally in aggregate form). In some embodiments aWG can be made using a wetting agent (e.g., a surfactant such asSoprophor) and a dispersant (e.g., a lignosulfonate such as Reax 88B,etc.). As described above in the Formulating Agents section, a widevariety of formulating agent(s) and various concentrations of wettingagents, dispersants, fillers and other formulating agents can be used toprepare exemplary formulations, e.g. wettable granules.

In addition to the various polymer nanoparticles described above,exemplary polymer nanoparticles are made from a co-polymer ofmethacrylic acid and ethyl acrylate at a 90:10 mass ratio. In someembodiments, the polymer nanoparticles are made from a co-polymer ofmethacrylic acid and styrene at a 90:10 mass ratio. In some embodiments,the polymer nanoparticles are made from a co-polymer of methacrylic acidand butylmethacrylate at a 75:25 mass ratio. In some embodiments, thepolymer nanoparticles are made from a co-polymer of acrylic acid andstyrene at a 75:25 mass ratio. In some embodiments, the polymernanoparticles are made from a co-polymer of acrylic acid and styrene ata 90:10 mass ratio. In some embodiments, the polymer nanoparticles aredispersed in a common solvent, in some cases at a concentration of 20mg/mL or higher. As described above in the Nanoparticles ofpolymer-associated active ingredient section, many ratios of co-polymerconstituents can be used.

In some exemplary embodiments, the active ingredient is selected fromazoxystrobin, fenamidone, fluoxastrobin, kresoxim methyl, pyraclostrobinand trifloxystrobin. In some embodiments, the ratio of active ingredientto polymer nanoparticle is 1:1, 2:1, 3:1, 4:1 or 5:1, a range betweenthese values or another range as listed above. As described above in theNanoparticles of polymer-associated active ingredient section, manyratios of strobilurin to polymer can be used.

In some embodiments, the dispersion of polymer nanoparticles and activeingredient in a common solvent is slowly added to a vessel containing asecond solvent, preferably water. In some embodiments, the secondsolvent is at least 20 times larger in volume than the common solventcontaining the polymer nanoparticles and active ingredient. In someembodiments, the second solvent contains a dispersant, preferably butnot limited to a lignosulfonate such as Reax 88B and/or a wetting agent,preferably but not limited to a surfactant such as sodium dodecylbenzenesulfonate and an inert filler, preferably but not limited to lactose.

In some embodiments, after the dispersion in a common solvent is mixedwith the second solvent the solvents are removed by drying. In someembodiments, the solvents are removed by freeze drying. In someembodiments, the solvents are removed by spray drying. The resultingsolid formulation is then moistened with about 30 to about 50%equivalent mass of water and is then extruded to form granules. In someexemplary embodiments, the granules are formed by hypodermic syringeextrusion. In some embodiments, the granules are formed throughextrusion granulation, pan granulation, fluid bed granulation, spraydrying granulation, or high shear granulation.

In some embodiments, the granules disperse in solution in 30 seconds orless. In some cases, the WG formulation has low friability. In someembodiments, the WG formulation has low dustiness. In some embodiments,when the WG formulation is dispersed in water, the dispersion results innanoparticles with an average size within about 100 to about 500 nm, orin some cases, within about 100 to about 200 nm. In some embodiments,when the WG formulation is dispersed in water, the dispersion results inparticles with an average size less than 100 nm. In some embodiments, adispersion of the WG formulation in water creates minimal foam. In someembodiments, the WG formulation is stable after 1-2 months of continuoustemperature cycling between −5° C. and 45° C. showing no visible signsof phase separation and can easily be dispersed in water at the userate.

In some embodiments, the current disclosure provides methods ofproducing WGs comprising low melting-point actives via extrusion of thegranules. In some embodiments, the active has a melting point of lessthan about 100° C., less than about 90° C., less than about 80° C., lessthan about 70° C., less than about 60° C., less than about 50° C. orless than about 40° C. It is surprising that wettable granules oflow-melting point actives can be prepared via extrusion of the granules.As discussed above, the heat produced during extrusion generally leadsto complications, such as separation of the active ingredient. In someembodiments, the active ingredient of the wettable granules of thecurrent disclosure is picoxystrobin, pyraclostrobin, orysastrobin,metominostrobin or trifloxystrobin.

Wettable Powder (WP)

In some embodiments, the dried solid can be made into a formulation thatis a wettable powder (WP). In some embodiments, a WP formulationcomprising nanoparticles of polymer-associated active ingredients(optionally in aggregate form) can be made from a dried (e.g., spraydried, freeze dried, etc.) dispersion of polymer nanoparticles andactive ingredient. In some embodiments, a WP formulation comprisingnanoparticles of polymer-associated active ingredients (optionally inaggregate form) can be made from a milled solid comprising polymernanoparticles of active ingredient. In some embodiments, a WP is made bymixing the dried solid with a dispersant and/or a wetting agent. In someembodiments, a WP is made by mixing the dried solid or milled solid witha dispersant and/or a wetting agent. In some embodiments, a WP is madeby mixing the dried or milled solid with a dispersant and a wettingagent. In some embodiments, the formulation of the final WP can be (byweight): up to about 98% nanoparticles of polymer-associated activeingredients (including both the active ingredient and the polymer,optionally in aggregate form). In some embodiments, the WP formulationincludes (by weight): 0-5% dispersant, 0-5% wetting agent, 5-98%nanoparticles of polymer-associated active ingredients (optionally inaggregate form), and inert filler to 100%. In some embodiments, theformulation of the final WP can be (by weight): 0.5-5% dispersant,0.5%-5% wetting agent, 5-98% nanoparticles of polymer-associated activeingredients (optionally in aggregate form), and inert filler to 100%. Asdescribed above in the Formulating Agents and Nanoparticles ofpolymer-associated active ingredient sections, a wide variety offormulating agent(s) and various concentrations of nanoparticles(including aggregates), wetting agents, dispersants, fillers and otherformulating agents can be used to prepare exemplary formulations, e.g.wettable granules.

In some embodiments, the formulation of the final WP can be (by weight):0.5-5% dispersant, 0.5%-5% wetting agent, 0.1-10% thickener (e.g., fumedsilica which, as noted above may serve multiple functions, and/orxanthan gum), 5-98% nanoparticles of polymer-associated activeingredients (optionally in aggregate form). As described above in theFormulating Agents section, a wide variety of formulating agent(s) andvarious concentrations of wetting agents, dispersants, fillers and otherformulating agents can be used to prepare exemplary formulations, e.g.wettable powders.

In some exemplary embodiments, described in more detail below, a WPformulation comprising nanoparticles of polymer-associated activeingredients (optionally in aggregate form) may be made from a dispersionof polymer nanoparticles and active ingredient in a common solvent,preferably methanol. In some embodiments, the a WP formulation can bemade by adding the dispersion in common solvent into a 1× Phosphatebuffered saline (PBS) solution, and then drying (e.g., freeze drying,spray drying etc) the resulting mixture to form a solid powder. In someembodiments, a WP formulation can be made by adding the dispersion incommon solvent into an aqueous solution containing a wetting agent(e.g., a surfactant such as sodium dodecylbenzene sulfonate) and/or adispersant (e.g., a lignosulfonate such as Reax 88B, etc.) andoptionally an inert filler (e.g., lactose), and then drying (e.g.,freeze drying, spray drying, etc.) the resulting mixture to from a solidpowder. In some embodiments a WP can be made using a wetting agent(e.g., a surfactant such as sodium dodecylbenzene sulfonate) and adispersant (e.g., a lignosulfonate such as Reax 88B, etc.).

In some exemplary embodiments, also described in more detail below, thepolymer nanoparticles are made from a co-polymer of methacrylic acid andethyl acrylate at about a 90:10 mass ratio. In some embodiments, thepolymer nanoparticles are dispersed in a common solvent, preferably at aconcentration of 20 mg/mL. In some embodiments, the polymernanoparticles are made from a co-polymer of methacrylic acid and styreneat about at a mass ratio of 75:25. In some embodiments, the polymernanoparticles are made from a co-polymer of acrylic acid and styrene atabout a 75:25 mass ratio. In some embodiments, the polymer nanoparticlesare made from a co-polymer of acrylic acid and styrene at about a 90:10mass ratio. In some embodiments, the active ingredient is azoxystrobinand is mixed into the polymer nanoparticle dispersion at a concentrationof 20 mg/mL. As described above in the Nanoparticles ofpolymer-associated active ingredient section, many ratios of co-polymerconstituents can be used.

In some embodiments, the dispersion of polymer nanoparticles and activeingredient is then slowly added into a vessel containing a secondsolvent, preferably water. In some embodiments, the second solvent is atleast 20 times larger in volume than the common solvent containing thepolymer nanoparticles and active ingredient. In some embodiments, thesecond solvent contains 1×PBS. In some embodiments, the second solventcontains a dispersant, preferably a lignosulfonate such as Reax 88Band/or a wetting agent, preferably a surfactant such as sodiumdodecylbenzene sulfonate. In some embodiments a WP can be made using awetting agent (e.g., a surfactant such as sodium dodecylbenzenesulfonate) and a dispersant (e.g., a lignosulfonate such as Reax 88B,etc.).

In some embodiments, after the dispersion of polymer nanoparticles andactive ingredient in a common solvent is mixed with a second solventcontaining dispersant and/or wetting agent, the final mixture is dried(e.g., freeze dried) to obtain a solid powdered formulation containingnanoparticles of polymer-associated active ingredients (optionally inaggregate form).

High Solids Liquid Suspension (HSLS)

One type of formulation that can be utilized according to the disclosureis a high solids liquid suspension. As described, such a formulation isgenerally characterized in that it is a liquid formulation that containsat least nanoparticles of polymer nanoparticles associated with activeingredient (includes potentially aggregates of the same).

In some embodiments, the formulation of the HSLS can be (by weight):between about 5 and about 80% nanoparticles of polymer-associated activeingredients (including both polymer and active ingredient, optionally inaggregate form), 0.5 and about 5% wetting agent and/or dispersant,between about 1 and about 10% anti-freezing agent, between about 0.2 andabout 10% anti-settling agent or thickener, between about 0.1 and about10% anti-foaming agent, between about 0.01 and about 0.1% preservativeand water up to 100% As described above in the Formulating Agents andNanoparticles of polymer-associated active ingredient sections, a widevariety of formulating agent(s) and various concentrations ofnanoparticles (including aggregates), wetting agents, dispersants,fillers and other formulating agents can be used to prepare exemplaryformulations, e.g., a HSLS.

In some exemplary embodiments, described in more detail below, thepolymer nanoparticles are made from a co-polymer of methyl methacrylicacid and ethyl acrylate at a 90:10 mass ratio. In some embodiments, thepolymer nanoparticles are dispersed in the common solvent, preferably ata concentration of 20 mg/mL. In some embodiments, the active ingredientis azoxystrobin, fenamidone, fluoxastrobin, kresoxim methyl,picoxystrobin, pyraclostrobin or trifloxystrobin and is mixed into thenanoparticle dispersion at a concentration of 20 mg/mL. As describedabove in the Nanoparticles of polymer-associated active ingredientsection, many ratios of co-polymer constituents can be used.

In some embodiments, the dispersion of polymer nanoparticles and activeingredient in a common solvent is slowly added into a vessel containinga second solvent, preferably water. In some embodiments, the secondsolvent is at least 20 times larger in volume than the common solventcontaining the polymer nanoparticles and active ingredient. In someembodiments, the second solvent contains a dispersant, preferably alignosulfonate such as Reax 88B and/or a wetting agent, preferably asurfactant such as sodium dodecylbenzene sulfonate. In some embodimentsa HSLS can be made using a wetting agent (e.g., a surfactant such assodium dodecylbenzene sulfonate) and a dispersant (e.g., alignosulfonate such as Reax 88B, etc.).

In some embodiments, the HSLS formulations of current disclosure have anactive ingredient content of about 5 to about 40% by weight, e.g., about5-about 40%, about 5-about 35%, about 5-about 30%, about 5-about 25%,about 5-about 20%, about 5-about 15%, about 5-about 10%, about 10-about40%, about 10-about 35%, about 10-about 30%, about 10-about 25%, about10-about 20%, about 10-about 15%, about 15-about 40%, about 15-about35%, about 15-about 30%, about 15-about 25%, about 15-about 20%, about20-about 40%, about 20-about 35%, about 20-about 30%, about 20-about25%, about 25-about 40%, about 25-about 35%, about 25-about 30%, about30-about 40% or about 35-about 40%. As described above in theNanoparticles of polymer-associated active ingredient section, manyratios of strobilurin to polymer can be used.

In some embodiments the HSLS formulations of current disclosure have anactive ingredient content of about 5%, about 10%, about 15%, about 20%,about 25%, about 30%, about 35% or about 40% by weight.

Methods of Making HSLS—Generally

In some embodiments, a HSLS comprising nanoparticles ofpolymer-associated active ingredient (optionally in aggregate form) canbe made from a dispersion of polymer nanoparticles and active ingredientin a common solvent or from a dried form of the dispersion (e.g., spraydried). In some embodiments, a HSLS formulation comprising nanoparticlesof polymer-associated active ingredients (optionally in aggregate form)can be made from a milled solid comprising polymer nanoparticles ofactive ingredient.

Methods of Making HSLS—Milling Methods

In some embodiments, a HSLS formulation comprising nanoparticles ofpolymer-associated active ingredients (optionally in aggregate form) canbe prepared via milling. Several exemplary methods and the resultingHSLS formulations are described below and in the Examples. In someembodiments, a solid formulation of nanoparticles of polymer-associateactive ingredient (optionally in aggregate form), prepared as describedin this disclosure (e.g., via milling, spray drying etc.) may be furthermilled in the presence of one or more formulating agents and water. Insome embodiments a HSLS can be made by milling a solid formulationnanoparticles of polymer-associated active ingredients in the presencewater and one more of an anti-freezing agent, (optionally more than oneof) a wetter and/or dispersant, an antifoaming agent, a preservative,and a thickening agent. Further, In some embodiments, the activeingredient and polymer nanoparticles are milled together to producecomprising nanoparticles of polymer-associated active ingredients, whichmay then be further milled according to the processes described below.

In some embodiments, the milling process is performed in separate phases(i.e., periods of time), with the optional addition of one or moreformulating agent between each milling phase. One of ordinary skill inthe art can adjust the length of each phase as is appropriate for aparticular instance. In some embodiments, the contents of the millingvessel are cooled between one or more of milling phases (e.g., viaplacement of the milling jar in an ice bath). One of ordinary skill inthe art can adjust the length of cooling period as is appropriate for aparticular instance.

In some embodiments, a HSLS can be made by first milling a solidformulation of nanoparticles of polymer-associated active ingredients inthe presence of (optionally more than one of) a wetter and/or dispersantin one milling vessel for a certain amount of time (e.g., about 30minutes-about 1 day), then this mixture is transferred to anothermilling vessel containing water and optionally one or more of ananti-freezing agent, additional wetter and/or dispersant, ananti-freezing agent, an antifoaming agent, a preservative, a thickeningagent, and milling the components together. As described above in theFormulating Agents section, a wide variety of additional formulatingagent(s) and various concentrations of wetting agents, dispersants,fillers and other formulating agents can be used in preparation ofexemplary formulations.

In some embodiments, a HSLS formulation comprising nanoparticles ofpolymer-associated active ingredients (optionally in aggregate form) canbe prepared via milling pre-formed polymer nanoparticles and activeingredient in the presence of one or more formulating agents and water.In some embodiments, a HSLS can be made by milling preformed polymernanoparticles and active ingredient in the presence of water andoptionally one more of an anti-freezing agent, additional wetter and/ordispersant, an anti-freezing agent, an antifoaming agent, apreservative, and a thickening agent. Again, as described above in theFormulating Agents section, a wide variety of additional formulatingagent(s) and various concentrations of wetting agents, dispersants,fillers and other formulating agents can be used in preparation ofexemplary formulations.

And as in the embodiment described above in which nanoparticles ofpolymer-associated active ingredients are milled in a two milling vesselprocedure, such a procedure can be used in preparing a HSLS frompre-formed polymer nanoparticles. In some embodiments such an HSLS canbe made by first milling a solid formulation nanoparticles ofpolymer-associated active ingredients in the presence of (optionallymore than one of) a wetter and/or dispersant in one milling vessel for acertain amount of time (e.g., about 30 minutes-about 1 day),transferring the milled components to another milling vessel containingwater and optionally one or more of an anti-freezing agent, additionalwetter and/or dispersant, an anti-freezing agent, an antifoaming agent,a preservative and a thickening agent.

Milling methods to produce HSLS formulations as described above mayinclude any of those referred to in any other portion of thespecification including the Examples below. Any type of mill noted inany portion of the specification may also be used to prepare HSLSformulations via milling.

Methods of Making HSLS—Mixing & Drying Methods

In some embodiments, a HSLS formulation is prepared without milling, butinstead by mixing the components of the formulation. These methods mayalso include drying the formulations to increase the solids content ofthe formulation so that it is suitable as a HSLS. All of these methodsare described in more detail below and exemplary methods are shown inthe Examples.

In some embodiments, a HSLS formulation comprising nanoparticles ofpolymer-associated active ingredients (optionally in aggregate form) canbe made from the dispersion of polymer nanoparticles and activeingredient in a common solvent, (e.g., methanol). In some embodiments,the dispersion is added to an aqueous solution containing a wettingagent and a dispersant, an anti-freezing agent (and optionally ananti-settling agent or thickener and a preservative). The mixture isthen concentrated by removing solvent, e.g., by drying, until thedesired high solids formulation is attained.

In some exemplary embodiments, after the dispersion of polymernanoparticles and active ingredient in a common solvent is mixed with asecond solvent containing a wetting agent and/or dispersant and ananti-freezing agent (optionally with an anti-settling agent or thickenerand a preservative), the final mixture is concentrated by removing mostof the common solvent and second solvent until a final formulation witha target solids content (e.g., at least 60% solids) is obtained. In someembodiments, the method used to concentrate the solution is vacuumevaporation. In some embodiments, a second solvent containing a wettingagent and/or dispersant and an anti-freezing agent (optionally with ananti-settling agent or thickener and a preservative) are added after themixture has already been concentrated. As described above in theNanoparticles of polymer-associated active ingredient section, manyranges of solids content can be achieved.

In some embodiments, the dispersion of polymer nanoparticles and activeingredient in a common solvent is added to a second solvent to form asolution of nanoparticles of polymer-associated active ingredients(optionally in aggregate form). The second solvent is typically misciblewith the common solvent and is usually water, but in some embodiments,the second solvent can also be a mixture of water with a third solvent,usually an alcohol, preferably methanol or ethanol. In some embodiments,the second solvent or mixture of solvents is only partially misciblewith the common solvent. In some embodiments, the second solvent ormixture of solvents is not miscible with the common solvent. In someembodiments, the HSLS formulation is stable after 1-2 months ofcontinuous temperature cycling between −5° C. and 45° C. showing novisible signs of phase separation, remains flowable, and can easily bedispersed in water at the use rate.

In some embodiments, a HSLS is made by reconstituting the drieddispersion (e.g., freeze dried) of nanoparticles of polymer-associatedactive ingredients in water to obtain a formulation with a target solidscontent (e.g., at least 60% solids) is obtained and then adding ananti-freezing agent (and optionally a thickening agent and apreservative) to the final mixture. In some embodiments, a HSLS is madeby reconstituting the milled (e.g., ball-milled) solid of nanoparticlesof polymer-associated active ingredients in water to obtain aformulation with a target solids content (e.g., at least 60% solids) isobtained and then adding an anti-freezing agent (and optionally at leastone thickening agent (e.g., fumed silica and/or xanthan gum), anantifoaming agent and a preservative) to the final mixture. In someembodiments, the HSLS is made by homogenizing all the componentstogether. In some embodiments the HSLS is made by milling all thecomponents together.

In some embodiments, a HSLS is made by mixing the dried dispersion(e.g., spray dried) with a wetting agent, preferably a surfactant suchas sodium dodecylbenzene sulfonate, a solvent, preferably but notlimited to water, and/or a dispersant, preferably, but not limited to alignosulfonate such as Reax 88B, and an anti-freezing agent, preferablybut not limited to ethylene glycol, in a high sheer mixer until a stableHSLS is obtained. In some embodiments a wetting agent, preferably asurfactant such as sodium dodecylbenzene sulfonate, a solvent,preferably but not limited to water, and a dispersant, preferably, butnot limited to a lignosulfonate such as Reax 88B are included. In someembodiments, a preservative, preferably propionic acid and ananti-settling agent or thickener, preferably but not limited to fumedsilica and/or a water dispersible agent like xanthan gum are alsoincluded.

Use of Low Melting Point Actives in HSLS Formulations

In some embodiments, the current disclosure provides methods ofproducing HSLS formulations comprising low melting-point actives. Insome embodiments, the active has a melting point of less than about 100°C., less than about 90° C., less than about 80° C., less than about 70°C., less than about 60° C., less than about 50° C. or less than about40° C. The preparation of traditional suspension concentrates of lowmelting-point actives is a non-trivial process. As discussed previously,typical suspension concentrate formulation involves milling the activeingredient to generate particles of about 1 to about 10 microns followedby dispersion of these particles in an aqueous phase in presence ofsurfactants. The use of standard granulation equipment melts low-meltingpoint actives, complicating or precluding the size reduction process. Itis thus useful that HSLS formulations of low-melting point actives maybe prepared according to the current disclosure. It is also surprisingthat, in some embodiments, HSLS formulations can be prepared accordingto the present disclosure via milling of the active ingredient in thepresence of pre-formed polymer nanoparticles. In some embodiments, theactive ingredient of HSLS formulations of the current disclosure ispicoxystrobin, pyraclostrobin, orysastrobin, metominostrobin ortrifloxystrobin.

Efficacy and Application

General Applications and Efficacy

As noted previously and in the Examples, in some embodiments, thedisclosure provides formulations of strobilurin compounds that haveeither improved curative, preventative, translocation and/or systemicfungicidal properties. In some embodiments, the strobilurin formulationsof the present disclosure demonstrate improved preventative activitycompared to commercial formulations of the same active ingredient, whichsuggests that they may be applied at lower effective rates inpreventative applications. In some embodiments, the strobilurinformulations of the present disclosure demonstrate enhanced curativeproperties compared to commercial formulations of the same activeingredient, which suggests that they may be applied at lower effectiverates in curative applications. Without wishing to be limited by anytheory, it is thought that the enhanced curative properties are due toincreased foliar penetration or translocation of strobilurins formulatedaccording to the present disclosure compared to strobilurins ofcommercially available formulations. In some embodiments, thestrobilurin formulations of the current disclosure can be applied atlower effective rates than commercial formulations for the control offungal plant disease. In some embodiments, the strobilurin isazoxystrobin.

In general, different strobilurins are typically applied at differenteffective rates between 10-400 gram of active ingredient (e.g.strobilurin) per hectare depending on the efficacy of the strobilurin(e.g., absolute potency of the active and retention at the site ofactivity), as well as conditions related to the crop being treated, leaftype, environmental conditions, the species infesting the crop,infestation levels, and other factors. As discussed above, improvementsin the formulation according to the current disclosure, such asincreased UV stability, physical retention at the site of action,residual activity, systemic absorption, or enhanced curative orpreventative activity can reduce the user rates. Some embodimentsdemonstrate improvements over typical commercial formulation, whichsuggests that lower rates of effective application could be used. Insome embodiments, rates may range from between about 0.1 and about 400g/hectare, preferably between about 0.1 and about 200 g/hectare, morepreferably between about 0.1 and about 100 g/hectare, more preferablybetween about 0.1 and about 10 g/hectare or more preferably betweenabout 0.1 and about 1 g/hectare. In some embodiments, rates may rangefrom between about 1 g and about 400 g/hectare, preferably between about1 and about 200 g/hectare, more preferably between about 1 and about 100g/hectare, or more preferably between about 1 and about 10 g/hectare. Insome embodiments, rates may be any of the rates or ranges of rates notedin any other portion of the specification.

General Application & Comparison to Current Commercial Formulations

In some embodiments, the disclosure provides methods of usingformulations of nanoparticles of polymer-associated strobilurins. Insome embodiments, the formulations are used to inoculate a target areaof a plant. In some embodiments, the formulations are used to inoculatea part or several parts of the plant, e.g., the leaves, stem, roots,flowers, bark, buds, shoots, and/or sprouts.

In some embodiments, a formulation comprising nanoparticles ofpolymer-associated active ingredients and other formulating agents isadded to water (e.g., in a spray tank) to make a dispersion that isabout 10 to about 2,000 ppm in active ingredient. In some embodiments,the dispersion is about 10 to about 1,000 ppm, about 10 to about 500ppm, about 10 to about 300 ppm, about 10 to about 200 ppm, about 10 toabout 100 ppm, about 10 to about 50 ppm, about 10 to about 20 ppm, about20 to about 2,000 ppm, about 20 to about 1,000 ppm, about 20 to about500 ppm, about 20 to about 300 ppm, about 20 to about 200 ppm, about 20to about 100 ppm, about 20 to about 50 ppm, about 50 to about 2,000 ppm,about 50 to about 1,000 ppm, about 50 to about 500 ppm, about 50 toabout 300 ppm, about 50 to about 200 ppm, about 50 to about 100 ppm,about 100 to about 2,000 ppm, about 100 to about 1,000 ppm, about 100 toabout 500 ppm, about 100 to about 300 ppm, about 100 to about 200 ppm,about 200 to about 2,000 ppm, about 200 to about 1,000 ppm, about 200 toabout 500 ppm, about 200 to about 300 ppm, about 300 to about 2,000 ppm,about 300 to about 1,000 ppm, about 300 to about 500 ppm, about 500 toabout 2,000 ppm, about 500 to about 1,000 ppm, about 1000 to about 2,000ppm.

As used in the specification, inoculation of a plant with a formulationof the current disclosure may, in some embodiments, refer to inoculationof a plant with a dispersion (e.g., in water or an aqueous mediumoptionally further comprising other additive such as adjuvants,surfactants etc.) prepared from a formulation of the present disclosureas described above. It is to be understood that the term formulation mayalso encompass dispersions for applications as described (e.g.,inoculation of a plant). It should also be understood that methods thatdescribe the use of strobilurin formulations of the present disclosuree.g., “use of formulations of the present disclosure to inoculate aplant,” “use of the formulations of the present disclosure to controlfungal diseases” and the like, encompass the preparation of a dispersionof the active ingredient in water or an aqueous medium (optionallyfurther comprising other additives such as adjuvants, surfactants etc.)for the purpose of inoculating a plant.

In some embodiments, a dispersion is produced and used to inoculate aplant with active ingredient at less than about 75% of a use rate listedon a label of a currently available commercial product of the sameactive ingredient. In some embodiments, a dispersion is produced toinoculate a plant with active ingredient at less than about 60% of a userate listed on the label of a currently available commercial product ofthe same active ingredient. In some embodiments, a dispersion isproduced to inoculate a plant with active ingredient at less than about50% of a use rate listed on the label of a currently availablecommercial product of the same active ingredient. In some embodiments, adispersion is produced to inoculate a plant with active ingredient atless than 40% of a use rate listed on the label of a currently availablecommercial product of the same active ingredient. In some embodiments, adispersion is produced to inoculate a plant with active ingredient atless than 30% of a use rate listed on the label of a currently availablecommercial product of the same active ingredient. In some embodiments, adispersion is produced to inoculate a plant with active ingredient atless than 20% of a use rate listed on the label of a currently availablecommercial product of the same active ingredient. In some embodiments, adispersion is produced to inoculate a plant with active ingredient atless than 10% of a use rate listed on the labels of a currentlyavailable commercial product of the same active ingredient. In someembodiments, a dispersion is produced to inoculate a plant with activeingredient at less than 5% of the use rate listed on a label of acurrently available commercial product of the same active ingredient. Insome embodiments, the strobilurin formulations of the present disclosureare used to inoculate a plant at an active ingredient use rate that isabout 75%, about 60%, about 50%, about 40%, about 30%, about 20% orabout 10% of a use rate listed on the labels of currently availablefungicide products. Fungicide labels can be referenced from commercialsuppliers and are readily accessible and available.

As described in more detail below, labels of commercially availableformulations often provide ranges of active ingredient use rates tocontrol fungal disease. In some embodiments, formulations of the currentdisclosure may be used to control fungal disease at a range of activeingredient dose rates whose high and low values are about 75%, about60%, about 50%, about 40%, about 30%, about 20% or about 10% of the highand low dose rates of a range listed on the label of a commerciallyavailable product of the same active ingredient. In some embodiments,the high and low dose rates of a formulation of the current disclosureare both lower than the high and low dose rate by the same percentage.

In preferred embodiments, the formulations of the current disclosure maybe used to control fungal disease at an active ingredient use rate thatis lower than the minimum rate of a range of rates listed on the labelof a commercially available product. In some embodiments, a formulationsof the current disclosure may be used to control fungal disease at anactive ingredient use rate that is less than about 75%, less than about60%, less than about 50%, less than about 40%, less than about 30%, lessthan about 20% or less than about 10% of the minimum use rate of a rangeof rates listed on the label of a commercially available product.

Low Concentration Application

In some cases, a strobilurin formulation is applied to the plant at aconcentration below the strobilurin's solubility limit in water.Although the active ingredient is soluble in water at these lowconcentrations, the strobilurin's activity is still affected by the wayit is formulated. This is surprising as it demonstrates that thestrobilurin is still associated with the polymer particle even whenapplied below its solubility limit. At concentrations below thesolubility limits it is expected that the strobilurins would behave thesame, or at least in a very similar fashion, regardless of theformulations, especially with respect to biological functions describedabove. This is because the strobilurins are still hydrophobic and thus,thought to still have low soil mobility, lack systemic effects anddisplay the traits of traditional strobilurin and traditionalstrobilurin formulations.

In some embodiments, however, a formulation with nanoparticles oraggregates of nanoparticles of polymer associated strobilurin compoundis shown to be more active (e.g., have systemic or curative effects)than commercially available suspension concentrates of a strobilurinwhen applied at a use rate below the solubility limit. Comparativeexample is described below in the Examples section. In some embodiments,the strobilurin is azoxystrobin. In some embodiments, the polymernanoparticles associated with the strobilurin compound is made from acopolymer of methacrylic acid and ethyl acrylate at a mole ratio of{tilde over ( )}90:10 (MAA:EA) though other ratios, as described above,are applicable. In some embodiments, the formulation includes a wetter,dispersant and filler. In some embodiments, the formulation was appliedwith a foliar retention aid to enhance sticking to the plant surface. Insome embodiments, the foliar retention aid is partially hydrolyzedpoly(vinyl alcohol) such as the products marketed under the Gohsenolbrand.

Improved Translocation of Active

In some embodiments, the disclosure provides formulations of strobilurincompounds that have improved translocation properties e.g., as comparedto a commercially available concentrate of the same active ingredient(e.g., Amistar®). Though the specifics of a comparison test aredescribed in an Example below, generally, the exemplary procedure is asfollows: The basal portion of a corn leaf was inoculated with adispersion of strobilurin compound prepared from a commercialstrobilurin formulation or a formulation of the present disclosure. Inan exemplary embodiment azoxystrobin in a HSLS formulation according tothis disclosure was compared to Amistar®. The dispersions were preparedin 0.25 wt % induce solution at a specific strobilurin concentration(e.g., 200 or 500 ppm). After inoculation of the leaf the corn plant wasplaced in a growing chamber. Translocation was evaluated by harvestingthe leaf 24 hours after application and cutting off the tip of the leaf(untreated part of the leaf) from its apical section. Evaluation andharvesting were performed 3 or 7 days after application. One of ordinaryskill in the art can adjust the evaluation time (as well as otherparameters including concentration and dilution) as is appropriate for aparticular instance.

The amount of compound in the tip of the leaf was evaluated (e.g., viaextraction with organic solvent and HPLC quantification). The amount ofstrobilurin in the tip (removed section) of the leaf is expressed as apercentage of the dry mass of the tip of the leaf. Leaves that had beeninoculated with formulations prepared according to the presentdisclosure showed increased translocation compared to leaves inoculatedwith commercial formulations. In some embodiments, there was a largeramount of strobilurin compound in the tips of leaves inoculated withformulations of the present disclosure than leaves inoculated withcommercial formulations. In some embodiments, the tips of leavesinoculated with formulations of the present disclosure contained morestrobilurin (expressed as a percentage of the dry weight of cut, apicalsections of the leaves) than leaves inoculated with commerciallyavailable strobilurin formulations.

Without wishing to be limited by any theory, in some embodiments, theenhanced translocation properties of strobilurins of the presentdisclosure are thought to be due in part to enhanced foliar penetration.Without wishing to be limited by any theory, the enhanced translocationproperties of the present disclosure may also be due in part to improvedadhesion specificity, smaller particle size and improved waterdispersibility. As discussed above, many strobilurins suffer from weakcurative activity because they are non-systemic (e.g., they do nottranslocate). Again without wishing to be limited, the improved curativeactivity of formulations of the present disclosure may be due toimproved translocation properties. As discussed above, enhanced curativeactivity provides a number of advantages, such as the potential forapplication at reduced effective active ingredient use rates.

Rainfast Applications

In some embodiments, a strobilurin formulation is applied anddemonstrates rainfast properties, in that the active ingredient (e.g.,strobilurin) does not dissipate with rain, in comparison withcommercially available formulations of the same active. Though thespecifics of a comparison test are described in an Example below,generally, the exemplary procedure is as follows: a 1.7 cm cut disk of acole plant leaf (cabbage at ca. 7 leaf stage) was inoculated with astrobilurin by dipping the disk into a dispersion containing either acommercial strobilurin formulation or a strobilurin formulationaccording to the disclosure at a specific use rate (e.g., 50 ppmstrobilurin) along with 0.5% Spray Adjuvant (Supercharge) for 5 secondsand was allowed to air dry for 1-2 hours. In an exemplary embodiment,the formulation includes azoxystrobin in a HSLS formulation according tothis disclosure. Rainfastness was evaluated by dipping inoculated leafdisks (as described in the Example below) into deionized water for 5seconds, allowing the leaf to air dry for 2 hours. The amount ofstrobilurin that remains on the leaf is quantified. The amount ofstrobilurin that remains on the leaf is expressed as percentage biomassof the dried leaf. In some embodiments, strobilurin remains on the leafafter dipping into deionized water (rain treatment). In someembodiments, the formulations of the current disclosure show comparableor improved rainfast properties compared to leaves inoculated withcommercial formulations.

Hard Water/Fertilizer Applications

As described below, most traditional formulations produce solidparticles (floc) or a precipitate when mixed in with high salt, hardwater or fertilizer solutions. Surprisingly, a dispersed solidformulation of a strobilurin (e.g., azoxystrobin) of the currentdisclosure was stable (e.g., components, azoxystrobin and the salt,remained disperse, i.e., no visible sedimentation or floc) when mixedwith a concentrated/high salt solution (e.g., hard water, buffer,concentrated fertilizer formulation) for at least 3 hours. This was trueeven for waters with ionic strength as high as 8000 ppm Mg²⁺ (a.k.a.CIPAC “G” hard water). It is important to note that for such a mixtureto be useful for the end user, the mixture should remain stable (i.e.,no formation of sediments and/or flocs) within at least about 30-40minutes—which is typically the time it takes for the mixture to beapplied to the plant. It is surprising that the formulations of thepresent disclosure are stable in such high-salt conditions. Because thepolymers that are used in the nanoparticles of the present disclosureare negatively charged, a practitioner of the art would expect theformulations of the present disclosure to flocculate when mixed withsuch a high amount of divalent salt. Without being limited by theory, itis believed that the increased stability of the formulations of thepresent disclosure arises from the use of nanoparticulate polymers asthe delivery system and that if standard non-nanoparticle polymers wereused then flocculation would occur

Traditional solid or liquid formulations are not stable under conditionsof high ionic (i.e., a high salt solution) strength. Sources ofincreased ionic strength can include, for example, mineral ions that arepresent in the water that a formulation is dispersed in. For example, inmany cases the water that is available to a farmer is taken from ahigh-salt (“hard water”) source such as a well or aquifer. Water that agrower uses can be variably hard and is normally measured as Ca²⁺equivalents. Ranges of water salinity can be from {tilde over ( )}0 ppmCa²⁺ equivalent (deionized water) to 8000 ppm Ca²⁺ or more.

Other sources of increased ionic strength can include, for example,other chemicals or materials that dispersed in the spray tank waterbefore or after the addition of the fungicide formulation. Examples ofthis include mineral additives such as micronutrients (which can includee.g., B, Cu, Mn, Fe, Cl, Mo, Zn, S) or traditional N—P—K fertilizerswhere the nitrogen, phosphorus, or potassium source is in an ionic formas well as other agro-chemicals (e.g., pesticides, herbicides, etc.). Insome embodiments, the fertilizer can be 10-34-0 (N—P—K), optionallyincluding one or more of sulfur, boron and another micronutrient. Insome cases, the nitrogen source is in the form of urea or anagriculturally acceptable urea salt. The fertilizer can include e.g.,ammonium phosphate or ammonium thiosulphate.

In some embodiments described below in the Examples, the formulations ofthe current disclosure were mixed with a concentrated/high saltsolution. Though the specifics of the hard test are described inExamples below, generally, the exemplary procedure is as follows:Formulations described herein were mixed with different hard waterstandards, each with a different degree of hardness (e.g., CIPAC Hstandard water (in the example below: 634 ppm hardness, pH 6.0-7.0,Ca²⁺:Mg²⁺=2.5:1), CIPAC J standard water (6.34 ppm hardness, pH 6.0-7.0,Ca²⁺:Mg²⁺=2.5:1) and CIPAC G standard water (8000 ppm hardness, pH6.0-7.0, Mg²⁺)) at an active ingredient concentration of 200 ppm. Insome embodiments, the formulations dispersed well and were stable for atleast an hour, with no signs of the formation of flocs or sediments.

In some cases, the formulations of the present disclosure can be appliedsimultaneously with a high-salt solution or suspension such as amicronutrient solution, a fertilizer, pesticide, herbicide solution, orsuspension (e.g., in furrow application). The ability to mix and applystrobilurins with other agricultural ingredients such as liquidfertilizers is very useful to growers, as it reduces the number ofrequired trips across crop fields and the expenditure of resources forapplication. In some cases, the formulations of the present disclosuremay be mixed with liquid fertilizers of high ionic strength. In somecases the fertilizer is a 10-34-0 fertilizer, optionally including oneor more of sulfur, boron and another micronutrient. In some cases, thenitrogen source is in the form of urea or an agriculturally acceptableurea salt. In some embodiments, the liquid fertilizer comprises aglyphosate or an agriculturally acceptable salt of glyphosate (e.g.,ammonium, isopropylamine, dimethylamine or potassium salt). In someembodiments, the liquid fertilizer may be in the form of a solution or asuspension. In some embodiments, formulations of the present disclosureare stable when mixed with liquid fertilizers of increased or high ionicstrength (e.g., at any of the ionic strengths described below). In someembodiments, when mixed with liquid fertilizers formulations of thecurrent disclosure show no signs of sedimentation or flocculation. Insome embodiments, the strobilurin is azoxystrobin.

Other potential additives that might be added into a spray tank that arecharged and can decrease the stability of an agrochemical formulationinclude charged surfactants or polymers, inert ingredients such as urea,or other similar ingredients.

In some embodiments, the present disclosure provides compositions of aformulation of nanoparticles of polymer-associated active ingredientsthat are redispersible in solutions with high ionic strength. In someembodiments, the present disclosure also provides compositions of aformulation of nanoparticles of polymer-associated active ingredientsthat can be redispersed in water and then have a high salt solution orsolid salt added and maintain their stability. In some embodiments, theformulations of the present disclosure are stable when dispersed in ordispersed in water and then mixed with solutions with ionic strengthcorresponding to Ca²⁺ equivalents of about 0 to about 1 ppm, about 0 toabout 10 ppm, about 0 to about 100 ppm, about 0 to about 342 ppm, about0 to about 500 ppm, about 0 to about 1000 ppm, about 0 to about 5000ppm, about 0 to about 8000 ppm, about 0 to about 10000 ppm, about 1 toabout 10 ppm, about 1 to about 100 ppm, about 1 to about 342 ppm, about1 to about 500 ppm, about 1 to about 1000 ppm, about 1 to about 5000ppm, about 1 to about 8000 ppm, about 1 to about 10000 ppm, about 10 toabout 100 ppm, about 10 to about 342 ppm, about 10 to about 500 ppm,about 10 to about 1000 ppm, about 10 to about 5000 ppm, about 10 toabout 8000 ppm, about 10 to about 10000 ppm, about 100 to about 342 ppm,about 100 to about 500 ppm, about 100 to about 1000 ppm, about 100 toabout 5000 ppm, about 100 to about 8000 ppm, about 100 to about 10000ppm, about 342 to about 500 ppm, about 342 to about 1000 ppm, about 342to about 5000 ppm, about 342 to about 8000 ppm, about 342 to about 10000ppm, about 500 to about 1000 ppm, about 500 to about 5000 ppm, about 500to about 8000 ppm, about 500 to about 10000 ppm, about 1000 to about5000 ppm, about 1000 to about 8000 ppm, about 1000 to about 10000 ppm,about 5000 to about 8000 ppm, about 5000 to about 10000 ppm, about 8000to about 10000 ppm.

Protective Use

In some embodiments, the present disclosure provides formulations ofstrobilurins that may be used as protective fungicides (also referred toas protectants). In general, protective fungicides are used to preventthe establishment of a pathogenic fungal infection in a plant or aportion of a plant. It is therefore desirable for the protectantfungicide to be present on the plant or portion of the plant prior toits contact with the pathogen. When used as protective fungicides, theformulations of the present disclosure may be used to make dispersionsof active ingredients as described above, at active ingredientconcentrations that correspond to any of the values or ranges above inthe Efficacy and Application or in other parts of this disclosure. Insome embodiments, a dispersion is prepared and used to inoculate a plantwith a protective fungicide at less than about 75% of a use rate listedon the label of a currently available commercial protective fungicideproduct of the same active ingredient. In some embodiments, a dispersionis prepared and used to inoculate a plant with a protective fungicide atless than about 60% of a use rate listed on the labels of a currentlyavailable commercial protective fungicide product of the same activeingredient. In some embodiments, a dispersion is prepared and used toinoculate a plant with a protective fungicide at less than about 50% ofa use rate listed on the label of currently available commercialprotective fungicide product. In some embodiments, a dispersion isprepared and used to inoculate a plant with a protective fungicide atless than about 40% of a use rate listed on the labels of currentlyavailable commercial protective fungicide products of the same activeingredient. In some embodiments, a dispersion is prepared and used toinoculate a plant with a protective fungicide at less than about 30% ofa use rate listed on the label of currently available commercialprotective fungicide products of the same active ingredient. In someembodiments, a dispersion is prepared and used to inoculate a plant witha protective fungicide at less than 20% of a use rate listed on a labelof a currently available commercial protective fungicide product of thesame active ingredient. In some embodiments, a dispersion is preparedand used to inoculate a plant with a protective fungicide at less thanabout 10% of a use rate listed on the label of a currently availablecommercial protective fungicide product of the same active ingredient.In some embodiments, a dispersion is prepared and used to inoculate aplant with a protective fungicide at less than 5% of a use rate listedon the label of currently available commercial protective fungicideproducts of the same active ingredient. In some embodiments, astrobilurin formulation of the current disclosure is used as aprotective fungicide at an active ingredient use rate that is about 75%,about 60%, about 50%, about 40%, about 30%, about 20% or about 10% ofthe use rate listed on the label of a currently available protectivefungicide product.

Labels of commercially available formulations often provide ranges ofactive ingredient use rates to control fungal disease. When used asprotectant fungicides as described above, a formulation of the currentdisclosure may be used to inoculate plants at an active ingredient userate that is less than about 75%, less than about 60%, less than about50%, less than about 40%, less than about 30%, less than about 20% orless than about 10% of the minimum use rate of a range of use rateslisted on the label of a commercially available product.

Curative Use

In some embodiments, the present disclosure provides formulations ofstrobilurins that have curative activity, and that may thus be used ascurative fungicides. In general, fungicides with curative activity maybe used to control established fungal infection in plants that are notyet showing visible symptoms of the infection. As such, fungicides withcurative activity can be applied to plants after the establishment ofinfection. When used as curative fungicides, the formulations of thepresent disclosure may be used to make dispersions of active ingredientsas described above, at active ingredient concentrations that correspondto any of the values or ranges above in the Efficacy and Application orin other parts of this disclosure. In some embodiments, a dispersion isprepared and used to inoculate a plant with a curative fungicide at lessthan about 75% of a use rate listed on the label of currently availablecommercial fungicide products of the same active ingredient. In someembodiments, a dispersion is prepared and used to inoculate a plant witha curative fungicide at less than about 60% of a use rate listed on thelabel of currently available commercial fungicide products of the sameactive ingredient. In some embodiments, a dispersion is prepared andused to inoculate a plant with a curative fungicide at less than about50% of a use rate listed on the label of currently available commercialfungicide products of the same active ingredient. In some embodiments, adispersion is prepared and used to inoculate a plant with a curativefungicide at less than about 40% of a use rate listed on the label ofcurrently available commercial fungicide products of the same activeingredient. In some embodiments, a dispersion is prepared and used toinoculate a plant with a curative fungicide at less than about 30% of ause rate listed on the label of currently available commercial fungicideproducts of the same active ingredient. In some embodiments, adispersion is prepared and used to inoculate a plant with a curativefungicide at less than about 20% of a use rate listed on the label ofcurrently available commercial fungicide products of the same activeingredient. In some embodiments, a dispersion is prepared and used toinoculate a plant with a curative fungicide at less than about 10% of ause rate listed on the label of currently available commercial fungicideproducts of the same active ingredient.

Labels of commercially available formulations often provide ranges ofactive ingredient use rates to control fungal disease. When used ascurative fungicides as described above, a formulations of the currentdisclosure may be used to inoculate plants at an active ingredient userate that is less than about 75%, less than about 60%, less than about50%, less than about 40%, less than about 30%, less than about 20% orless than about 10% of the minimum use rate of a range of use rateslisted on a commercially available product's label.

Dual Activity (Protective & Curative Uses)/Plant Health Applications

In some embodiments, the present disclosure provides formulations ofstrobilurins that have both protective and curative activity. Theseformulations can be used as protective fungicides, curative fungicides,or as fungicides in both protective and curative applications. Theseformulations can be used at concentrations and use rates that correspondto any of the values or ranges of values noted above or in otherportions of the Efficacy and Application Section.

In some embodiments, application of formulations of the presentdisclosure to plants (e.g., crop plants) of the present disclosureresults in a yield increase (e.g., increased crop yield). In someembodiments, there is a yield increase compared to untreated crops. Insome embodiments, there is an increase compared to crops that have beentreated with a commercial formulation of the same active ingredient. Insome embodiments, there is yield increase of about 2 to about 100%,e.g., 2-3%, 2-5%, 2-10%, 2-30%, 2-50%, 2-100%, 5-7%, 5-10%, 5-20%,5-30%, 5-40%, 5-50%, 5-60%, 5-70%, 5-80%, 5-90%, 5-100%, 10-20%, 10-30%,10-40%, 10-50%, 10-60%, 10-70%, 10-80%, 10- 90%, 20-40%, 20-60%, 20-80%,20-100%, 30-50%, 30-60%, 30-80%, 30-100%, 40-60%, 40-80%, 40-100%,50-80%, 50-100%, 60-80%, 60-100%, 70-90%, 70-100% or 80-100%

In some embodiments, the use of the strobilurin formulations of thepresent disclosure results in a yield increase of about 2%, about 3%,about 4%, about 5%, about 6%, about 7%, about 10%, about 20%, about 30%,about 40%, about 50%, about 60%, about 70%, about 80%, about 90% orabout 100%. In some embodiments, there is yield increase of greater thanabout 2%, greater than about 5%, greater than about 10%, greater thanabout 20%, greater than about 30%, greater than about 40%, greater thanabout 50%, greater than about 60%, greater than about 70%, greater thanabout 80%, greater than about 90% or greater than about 100%. In someembodiments, the use of the strobilurin formulations of the presentdisclosure in plant health applications results in a yield increase ofgreater than about 10%, greater than about 20%, greater than about 30%,about 40%, about 50%, about 60%, about 70%, about 80%, about 90% orabout 100%. In some embodiments, there is an increase in yield ofgreater than about 10%, greater than about 20%, greater than about 30%,greater than about 40%, greater than about 50%, greater than about 60%,greater than about 70%, greater than about 80%, greater than about 90%or greater than about 100%. Yield increases may be relative to untreatedcontrol plants (e.g., plants that have not been treated withformulations of the present disclosure), or plants treated withcurrently available commercial products.

In some embodiments, inoculation of plants with formulations of thepresent disclosure provides an increased crop yield as described above,at an active ingredient use rates that are lower than the use rateslisted on commercially available products of the same active ingredient.In some embodiments, the increased yield can correspond to any of thevalues or ranges of values noted above. In some embodiments, theincreased yield is observed at an active ingredient use rate that isless than about 75%, less than 60%, less than 50%, less than 40%, lessthan 30%, less than 20% or less than 10% of a rate listed on the labelof commercially available fungicide product of the same activeingredient. In some embodiments, the increased yield is observed at anactive ingredient use rate that is about 75%, about 60%, about 50%,about 40%, about 30%, about 20% or about 10% of a rate listed on a labelof a commercially available fungicide product of the same activeingredient. Labels of commercially available formulations often provideranges of active ingredient use rates to inoculate plants. In someembodiments, inoculation of plants with a formulation of the presentdisclosure provides an increased crop yield at an active ingredient userate that is lower than the minimum use rate of a range of use rateslisted on the label of a commercially available product. In someembodiments inoculation of plants with a formulation of the presentdisclosure provides an increased crop yield at a use rate that is lessthan about 75%, less than about 60%, less than about 50%, less thanabout 40%, less than about 30%, less than about 20% or less than about10% of the minimum use rate of a range of use rates listed on the labelof a commercially available product.

Without wishing to be limited by any theory, in some embodiments, it isthought that increased yield is due enhanced plant health of plantstreated with formulations of the present disclosure. As used herein,plant health refers to the overall condition of the plant, including itssize, sturdiness, optimum maturity, consistency in growth pattern andreproductive activity. As mentioned above, optimizing and enhancing suchfactors is a goal of plant breeders. As used herein, increased orenhanced plant health can also refer to increased yield of one sample orset of crops (e.g., a crop field treated with fungicide) compared toanother sample or set of the same crops (e.g., an untreated crop field).

The enhancement of plant health by applications of strobilurinfungicides is thought to be due to a number of factors, as discussedabove. These include combating hidden and undiagnosed diseases, as wellas and the triggering of plant growth regulators (the strobiluringreening effect, see D. W. Bartlett, J. M. Clough, J. R. Godwin, A. A.Hall, M. Hamer, and B. Parr-Dobrzanski. Pest Manag. Sci. 2002, 58. 649).In some embodiments, the strobilurin formulations of the presentdisclosure can be used to enhance plant health at an active ingredientuse rate that is lower than the rate listed on the labels of currentlyavailable commercial curative fungicide products of the same activeingredient. In some embodiments, a strobilurin formulations of thepresent disclosure is used to inoculate a plant at an active ingredientuse rate that is less than about 75%, less than about 60%, less thanabout 50%, less than about 40%, less than about 30%, less than about 20%or less than about 10% of a use rate listed on the label of a currentlyavailable fungicide product. In some embodiment, a strobilurinformulation of the present disclosure is used to inoculate a plant at anactive ingredient use rate that is about 75%, about 60%, about 50%,about 40%, about 30%, about 20% or about 10% of a use rate listed on thelabel of a currently available fungicide product. Labels of commerciallyavailable formulations often provide ranges of active ingredient userates to inoculate plants. In some embodiments, a formulation of thecurrent disclosure is used to inoculate plants at an active ingredientuse rate that is lower than the minimum use rate of a range of use rateslisted on the label of a commercially available product. In someembodiments a formulation of the current disclosure is used to inoculateplants at a use rate that is less than about 75%, less than about 60%,less than about 50%, less than about 40%, less than about 30%, less thanabout 20% or less than about 10% of the minimum use rate of a range ofuse rates listed on the label of a commercially available product

Without wishing to be limited by any theory, in some embodiments, it isthought that the formulations of the present disclosure can be used toenhance plant health at an active ingredient use rate that is lower thanthe rate listed on commercially available products of the same activeingredient due to their enhanced curative and preventative properties.Without wishing to be limited by any theory, it is though that in someembodiments, the enhanced curative properties are due to enhanced foliarpenetration and/or translocation. Without wishing to be limited by anytheory it is thought that in some embodiments, the formulations of thepresent disclosure are more effective at combating hidden diseasebecause of their enhanced residual activity, which increases the windowof opportunity for successful application timing.

Direct Soil & Seed Applications

In some embodiments, formulations of the current disclosure may be usedto control fungal disease of plants (including seeds) by application tosoil (inoculation of soil). The formulations of the current disclosuremay be used to control fungal disease via application to the soil inwhich a plant is to be planted prior to planting (i.e., as pre-plantincorporated application). In some embodiments, the formulations of thepresent disclosure are used to control fungal disease via inoculation ofthe seed and soil at the time of seed planting (e.g., via an in-furrowapplication or T-banded application). The formulations of the currentdisclosure may also be applied to soil after planting but prior toemergence of the plant (i.e., as a pre-emergence application). In someembodiments, soil is inoculated with a formulation of the currentdisclosure via an aerosol spray or pouring.

In some embodiments, the strobilurin formulations of the currentdisclosure may be used to control fungal diseases in the aforementionedapplications at an active ingredient use rate that is lower than the userate listed on the labels of commercially available formulations of thesame active ingredient, as described above. In some embodiments, aformulation of the present disclosure is used to control fungal diseaseat an active ingredient use rate that is less than about 75%, less thanabout 60%, less than about 50%, less than about 40%, less than about30%, less than about 20% or less than about 10% of a use rate listed onthe labels of currently available commercial strobilurin products of thesame active ingredient. In cases in which labels of commerciallyavailable formulations provide ranges of active ingredient use rates tocontrol fungal disease, in some embodiments, a formulations of thecurrent disclosure are used to control fungal disease at an activeingredient use rate that is lower than the minimum use rate of the rangeof use rates listed on the commercially available product's label. Insome embodiments a formulation of the current disclosure is used tocontrol fungal disease at a use rate that is less than about 75%, lessthan about 60%, less than about 50%, less than about 40%, less thanabout 30%, less than about 20% or less than about 10% of the minimum userate of a range of use rates listed on the label of a commerciallyavailable product.

In some embodiments, the strobilurin formulations of the currentdisclosure can be used to control fungal disease when applied to seeds.In some embodiments, the formulations of the current disclosure are usedto control fungal disease when applied to seeds at an active ingredientuse rate that is less than the use rate of commercially availableformulations of the same active ingredient. In some embodiments, aformulation of the present disclosure is used to control fungal diseaseswhen applied to seeds at an active ingredient use rate that is less thanabout 75%, less than about 60%, less than about 50%, less than about40%, less than about 30%, less than about 20% or less than about 10%, ofa use rate listed on the label of a currently available commercialstrobilurin product of the same active ingredient. In some embodiments,a formulation of the present disclosure are used to control fungaldisease when applied to seeds at an active ingredient use rate that isabout 75%, about 60%, about 50%, about 40%, about 30%, about 20% orabout 10%, of a rate listed on the label of a currently availablestrobilurin product of the same active ingredient. In some embodiments,commercially available products provide ranges of active ingredient userates to control fungal disease when applied to seeds. In someembodiments, the formulations of the current disclosure are used tocontrol fungal disease when applied to seeds at an active ingredient userate that is lower than the minimum use rate of a range of use rateslisted on a commercially available product's label. In some embodimentsa formulation of the current disclosure is used to control fungaldisease when applied to seeds at a use rate that is less than about 75%,less than about 60%, less than about 50%, less than about 40%, less thanabout 30%, less than about 20% or less than about 10% of the minimum userate of a range of use rates listed on the label of a commerciallyavailable product.

Increased Re-Application Interval

Due to their enhanced curative and preventative properties, in someembodiments, the formulations of the present disclosure can be appliedat greater time intervals (i.e., the time between distinct inoculations)than currently available formulations of the same active ingredient.Inoculation intervals can be found on the labels of currently availablecommercial formulations and are readily accessible and available. Insome embodiments, the formulations of the present disclosure are appliedat an interval that is 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days or 15days longer than commercial formulations of the same active ingredient.In some cases, commercial formulations are applied at intervals thatcorrespond to a range of intervals (e.g., 7-14 days). In such cases, itis contemplated that the formulations of the present disclosure can beapplied at a range of intervals whose shortest endpoint, longestendpoint, or both shortest and longest endpoint are longer than thecorresponding endpoints of currently available commercial formulationsby any of the values noted above. In some embodiments, the strobilurinformulations of the present disclosure can be applied at an intervals of5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29days, 30 days, 31 days, 32 days, 33 days, 34 days, 35 days, 36 days, 37days, 38 days, 39 days or 40 days. In some embodiments, the formulationsof the present disclosure can be applied at a range from which theshortest and longest intervals (endpoints) are taken from any of theaforementioned values.

Specific Application (Plant & Fungi)

In some embodiments, the inoculation method is applied to individualplants or fungi, or to large groups of plants and fungi. In someembodiments, the formulation is inoculated to the target organism bymeans of dipping the target organism or part of the organism into thedispersion containing the formulation. In some embodiments, theformulation is inoculated to the target species (plant or fungi) bymeans of an aerosol spray. In some embodiments, the formulation isinoculated to the target species (plant) by spraying the dispersiondirectly onto the leaves, stem, bud, shoot or flowers of the plant. Insome embodiments, the formulation is inoculated to the target species(plant) by pouring the dispersion directly onto the root zone of theplant. In some embodiments, the target organism (e.g., the plant onwhich fungus is to be controlled or the fungus is inoculated by means ofdipping the plant or a part of parts of the target plant into adispersion of active ingredients prepared as described above.Formulations of the current invention can also be applied in conjunctionwith irrigation systems and via water for irrigation.

The strobilurin formulations of the present disclosure can be used tocontrol fungal disease of a variety of plants. In some embodiments, theplant is selected from the classes fabaceaae, brassicaceae, rosaceae,solanaceae, convolvulaceae, poaceae, amaranthaceae, laminaceae andapiaceae.

In some embodiments, the plant is selected from plants that are grownfor turf, sod, seed (e.g., grasses grown for seed), pasture orornamentals. In some embodiments, the plant is a crop, including but notlimited to cereals (e.g., wheat, maize, including field corn and sweetcorn, rice, barley, oats etc.), soybean, cole crops, tobacco, oil crops,cotton, fruits (e.g., pome fruits such as but not limited to apples andpears), vine crops (e.g., cucurbits), legume vegetables, bulbvegetables, rapeseed, potatoes, greenhouse crops, and all other crops onwhich strobilurins are known to control fungal disease. Lists of plantson which fungal diseases are controlled by specific commerciallyavailable strobilurin formulations can be found on their labels, whichare readily accessible and available. (Examples of such products aregiven below).

In some embodiments, the formulations of the current disclosure are usedto control fungal diseases in turf, ornamental and non-crop applications(uses). Examples of these applications can be found on the labels ofcurrently available strobilurin formulations, such as the labelsreferenced in other portions of the specification. Non-limiting examplesof turf, ornamental and non-crop applications in which the formulationsof the present disclosure can be used include the control of fungaldiseases of turf (e.g., lawns and sod) in residential areas, athleticfields, parks, and recreational areas such as golf courses. Formulationsof the present disclosure may also be used to control fungal diseases ofornamentals (e.g., shrubs, ornamental trees, foliage plants etc.),including ornamentals in or around any of the aforementioned areas, aswell as in greenhouses (e.g., those used for growth of ornamentals).Examples of fungi that can be controlled in turf, ornamental andnon-crop applications, include those listed as fungi turf, ornamentaland non-crop applications in any other portion of the specification orin any of the labels of currently available strobilurin products used tocontrol fungi in turf, ornamental and non-crop applications (such as thethose referenced in other portions of the specification).

In some embodiments, the fungus to be controlled by the formulations ofthe present disclosure is selected from the classes ascomycota,basidiomycota, deuteromycota, blastocladiomycota, chytridiomycota,glomeromycota and combinations thereof.

Examples of fungal diseases that can be controlled with formulations ofthe current disclosure include but are not limited to various blights,spots and rusts, rots, blasts and smuts and combinations thereof.

In some embodiments, the plant (e.g., crop) on which fungal disease canbe controlled by formulations of the present disclosure may depend on,among other variables, the active ingredient, inclusion of othercomponents into the formulation, and the particular application. Commoncommercial formulations frequently include labels and instructionsdescribing the compatibility of actives, inclusion of additives, tankmixes with other products (e.g., surfactants) labeled fungi,instructions and restrictions for particular applications and uses aswell as other information. Such labels and instructions pertinent to theformulations of the present disclosures and their application are alsocontemplated as part of the present disclosures. Labels are readilyaccessible from manufacturers' websites, or via centralized internetdatabases such as Greenbook (http://www.greenbook.net/) or the Crop DataManagement Systems website (www.cdms.net).

In some embodiments, the strobilurin of the present disclosure isazoxystrobin, trifloxystrobin, pyraclostrobin, pyraclostrobin, orfluoxastrobin.

Specific Commercial Applications (Crop, Active, Dose, Application &Formulation)

As used herein, “a range of rates” listed on the label of a commerciallyavailable product refers to a rate range listed for the control of apest or pests in a certain application (e.g. on a crop). For example,the labeled use rate for the control of Puccina sorghi on cotton byQuadris is 109-164 g/ha, which is a “range of rates.”

Azoxystrobin

In various embodiments, the azoxystrobin formulations of the currentdisclosure may be used to control fungal diseases at active ingredientuse rates that are lower than the use rates listed on the labels ofcommercially available azoxystrobin fungicides. In some embodiments, anazoxystrobin formulation of the current disclosure may be used tocontrol fungal disease at a use rate that is less than about 75%, lessthan about 60%, less than about 50%, less than about 40%, less thanabout 30%, less than about 20% or less than about 10% of a use ratelisted on the label of a commercially available azoxystrobin fungicideproduct.

Labels of commercially available azoxystrobin products often provideranges of active ingredient use rates to control certain fungal diseaseson certain plants (e.g., as shown in table 4, 109-282 g/ha for thecontrol of aerial blight of soybean). In some embodiments, theazoxystrobin formulations of the current disclosure are used to controlfungal disease at an active ingredient use rate that is lower than theminimum use rate of a range of use rates listed on the label of acommercially available azoxystrobin product. In some embodiments anazoxystrobin formulation of the current disclosure is used to controlfungal disease at a use rate that is less than about 75%, less thanabout 60%, less than about 50%, less than about 40%, less than about30%, less than about 20% or less than about 10% of the minimum use rateof a range of use rates listed on the label of a commercially availableazoxystrobin product.

Azoxystrobin—Soybeans

Labelled use rates for the control of various fungal diseases ofsoybeans by Quadris® and Priori®, two commercially availableazoxystrobin suspension concentrates, are provided in Table 4.

TABLE 4 Active ingredient use rates for the control of fungal diseasesof soybeans by commercially available azoxystrobin products. Use RateProduct Target Fungi (g ai/ha) Quadris ® Aerial blight (Rhizoctoniasolani), Anthracnose 109-282 (Colletotrichum truncatum), Alternaria leafspot (Alternaria spp.), Brown spot (Septoria glycines) Cercospora blightand leaf spot (Cercospora kikuchii), Frogeye leaf spot (Cercosporasojina), Pod and stem blight (Diaporthe phoseolorum), Rust (Phakopsoraspp.) Soilborne diseases: Southern blight (Sclerotium 9.7-19.3 g/rolfsii), Rhizoctonia solani (Rhizoctonia solani) 1000 row metersPriori ® Cercospora kikuchii, Phokopsora pachyrhizi, 50 Septoriaglycines

In some embodiments, the azoxystrobin formulations of the currentdisclosure are used to control fungal diseases of soybeans at an activeingredient use rate that is lower than the use rates listed on the labelof commercially available azoxystrobin fungicides. In some embodiments,an azoxystrobin formulation of the current disclosure is used to controlfungal diseases of soybeans at a use rate that is less than about 75% ofa rate listed on the label of a commercially available azoxystrobinfungicide product. In some embodiments, an azoxystrobin formulation ofthe current disclosure is used to control fungal diseases of soybeans ata use rate that is less than about 60% of a rate listed on the label ofa commercially available azoxystrobin fungicide product. In someembodiments, an azoxystrobin formulation of the current disclosure isused to control fungal diseases of soybeans at a use rate that is lessthan about 50% of a rate listed on the label of a commercially availableazoxystrobin fungicide product. In some embodiments, an azoxystrobinformulation of the current disclosure is used to control fungal diseasesof soybeans at a use rate that is less than about 40% of a rate listedon the label of a commercially available azoxystrobin fungicide product.In some embodiments, an azoxystrobin formulation of the currentdisclosure is used to control fungal diseases of soybeans at a use ratethat is less than about 30% of a rate listed on the label of acommercially available azoxystrobin fungicide product. In someembodiments, an azoxystrobin formulation of the current disclosure isused to control fungal diseases of soybeans at a use rate that is lessthan about 20% of a rate listed on the label of a commercially availableazoxystrobin fungicide product. In some embodiments, an azoxystrobinformulation of the current disclosure is used to control fungal diseasesof soybeans at a use rate that is less than about 10% of a rate listedon the label of a commercially available azoxystrobin fungicide product.

In some embodiments, the azoxystrobin formulations of the currentdisclosure are used to control fungal disease of soybeans at an activeingredient use rate that is lower than the minimum use rate of a rangeof use rates listed on a commercially available product's label. In someembodiments azoxystrobin formulations of the current disclosure is usedto control fungal disease at a use rate that is less than about 75%,less than about 60%, less than about 50%, less than about 40%, less thanabout 30%, less than about 20% or less than about 10% of the minimum userate of a range of use rates listed on the label of a commerciallyavailable product.

In some embodiments, the azoxystrobin formulations of the presentdisclosure may be used to control fungal diseases of soybeans at anactive ingredient use rate of about 82-about 212 g/ha, about 65-about169 g/ha, about 54-about 141 g/ha, about 44-about 113 g/ha, about33-about 85 g/ha, about 22-about 56 g/ha, or about 11-about 28 g/ha.

In some embodiments, the azoxystrobin formulations of the currentdisclosure may be used to control fungal diseases of soybeans at anactive ingredient use rate of less than about 212 g/ha, less than about169 g/ha, less than about 141 g/ha, less than about 113 g/ha, less thanabout 85 g/ha, less than about 82 g/ha, less than about 65 g/ha, lessthan about 56 g/ha, less than about 54 g/ha, less than about 44 g/ha,less than about 32 g/ha, less than about 28 g/ha, less than about 22g/ha, or less than about 11 g/ha. In some embodiments, the azoxystrobinformulations of the current disclosure can be used to control fungaldiseases of soybeans at an active ingredient use rates of less thanabout 50 g/ha, less than about 37.5 g/ha, less than about 30 g/ha, lessthan about 25 g/ha, less than about 20 g/ha, about 15 g/ha or less thanabout 10 g/ha.

Non-limiting examples of fungal diseases of soybeans that can becontrolled with formulations of the present disclosure are Aerial blight(Rhizoctonia solani), Anthracnose (Colletotrichum truncatum), Alternarialeaf spot (Alternaria spp.), Brown spot (Septoria glycines), Cercosporablight and leaf spot (Cercospora kikuchii), Frogeye leaf spot(Cercospora sojina), Pod and stem blight (Diaporthe phaseolorum) andRust (Phakopsora spp.).

In some embodiments, the azoxystrobin formulations of the currentdisclosure may be used to control soilborne fungal diseases of soybeansat an active ingredient use rate that is lower than the use rate listedon the label of commercially available azoxystrobin fungicides. In someembodiments, an azoxystrobin formulation of the current disclosure isused to control soilborne fungal diseases of soybeans at a use rate thatis about 75%, about 60%, about 50%, about 40%, about 30%, about 20% orabout 10% of a use rate listed on the label of commercially availableazoxystrobin fungicides.

In some embodiments, the azoxystrobin formulations of the currentdisclosure may be used to control soilborne fungal diseases of soybeansat an active ingredient use rate that is lower than the minimum use rateof a range of use rates listed on the commercially available product'slabel. In some embodiments an azoxystrobin formulation of the currentdisclosure is used to control soilborne fungal diseases of soybeans at ause rate that is less than about 75%, less than about 60%, less thanabout 50%, less than about 40%, less than about 30%, less than about 20%or less than about 10% of the minimum use rate of a range of use rateslisted on the label of a commercially available azoxystrobin product.

In various embodiments, the azoxystrobin formulations of the currentdisclosure may be used to control soilborne diseases of soybeans atactive ingredient use rates of about 7.3-about 14.5 g per 1000 rowmeters, about 5.8-about 11.6 g per 1000 row meters, about 4.8-about 9.7g per 1000 row meters, about 3.9-about 7.7 g per 1000 row meters, about2.9-about 5.8 g per 1000 row meters, about 1.9-about 3.9 g per 1000 rowmeters or about 1.0-about 1.9 g per 1000 row meters. In someembodiments, the azoxystrobin formulations of the current disclosure maybe used to control soilborne diseases of soybeans at active ingredientuse rates of about less than about 1.0 g per 1000 row meters, less thanabout 1.9 g per 1000 row meters, less than about 2.9 g per 1000 rowmeters, less than about 3.9 g per 1000 row meters, less than about 4.8 gper 1000 row meters, less than about 5.8 g per 1000 row meters, lessthan about 7.3 g per 1000 row meters, less than about 7.7 g per 1000 rowmeters, less than about 9.7 g per 1000 row meters, less than about 11.6g per 1000 row meters or less than about 14.5 g per 1000 row meters.

In various embodiments, the azoxystrobin formulations of the currentdisclosure may be used to control soilborne diseases of soybeans atactive ingredient use rates of about 7.3-about 14.5 g per 1000 rowmeters, about 5.8-about 11.6 g per 1000 row meters, about 4.8-about 9.7g per 1000 row meters, about 3.9-about 7.7 g per 1000 row meters, about2.9-about 5.8 g per 1000 row meters, about 1.9-about 3.9 g per 1000 rowmeters or about 1.0-about 1.9 g per 1000 row meters.

In some embodiments, the azoxystrobin formulations of the currentdisclosure may be used to control soilborne diseases of soybeans at anactive ingredient use rate of less than about 1.0 g per 1000 row meters,less than about 1.9 g per 1000 row meters, less than about 2.9 g per1000 row meters, less than about 3.9 g per 1000 row meters, less thanabout 4.8 g per 1000 row meters, less than about 5.8 g per 1000 rowmeters, less than about 7.3 g per 1000 row meters, less than about 7.7 gper 1000 row meters, less than about 9.7 g per 1000 row meters, lessthan about 11.6 g per 1000 row meters or about less than 14.5 g per 1000row meters.

Non-limiting examples of the types of soilborne diseases of soybeansthat can be controlled by azoxystrobin formulations of the presentdisclosure are Rhizoctonia solani and Southern blight (Sclerotiumrolfsii).

In some embodiments, the azoxystrobin formulations of the currentdisclosure are used for plant health applications on soybean at a userate that is lower than a use rate listed on the label of a commerciallyavailable azoxystrobin fungicide product. In some embodiments, theazoxystrobin formulations of the current disclosure are used for planthealth applications on soybean at a use rate that is lower than theminimum use rate of a range of use rates listed on the label of acommercially available azoxystrobin fungicide product. In someembodiments, an azoxystrobin formulation of the current disclosure isused at a rate that is less than about 75%, about 60%, about 50%, about40%, about 30%, about 20% or about 10% of the use rate (or the minimumuse rate of a range of use rates) listed on the label of a commerciallyavailable azoxystrobin fungicide product. When used for plant healthapplications, the azoxystrobin formulations of the present disclosurecan be used at active ingredient rates that correspond to any of thevalues or ranges of values noted above for the control of fungaldiseases on soybean.

In some embodiments, the use of the azoxystrobin formulations of thepresent disclosure in plant health applications on soybeans results in ayield increase (e.g., increased crop yield). In some embodiments, theyield increase corresponds to any of the values or ranges of valuesnoted above for yield increases due to plant health applications.

Azoxystrobin—Cereals

In some embodiments, the azoxystrobin formulations of the presentdisclosure are used to control fungal diseases of cereals at an activeingredient use rate that is lower than the use rates listed on the labelof commercially available azoxystrobin fungicides. In some embodiments,an azoxystrobin formulation of the current disclosure is used to controlfungal diseases of cereals at a use rate that is 75%, 60%, 50%, 40%,30%, 20%, or 10% of a use rate listed on the label of a commerciallyavailable azoxystrobin fungicide product.

Labels of commercially available azoxystrobin formulations often provideranges of active ingredient use rates to control fungal disease ofcereals. In some embodiments, the formulations of the current disclosureare used to control fungal disease at an active ingredient use rate thatis lower than the minimum use rate of a range of use rates listed on thecommercially available product's label. In some embodiments anazoxystrobin formulation of the current disclosure may be used tocontrol fungal disease at a use rate that is less than about 75%, lessthan about 60%, less than about 50%, less than about 40%, less thanabout 30%, less than about 20% or less than about 10% of the minimum userate of a range of use rates listed on the label of a commerciallyavailable product.

Examples of fungal diseases of cereals and corresponding activeingredient use rates for their control can be found on the labels ofcommercially available azoxystrobin fungicide products (e.g., Quadris®and Priori®). Examples of fungal diseases of cereals that can becontrolled with formulations of the present disclosure include but arenot limited to various blights, spots and rusts, rots, blasts and smuts.

In some embodiments, the azoxystrobin formulations of the currentdisclosure are used for plant health applications on cereals at a userate that is lower than a use rate listed on the label of a commerciallyavailable azoxystrobin fungicide product. In some embodiments, theazoxystrobin formulations of the current disclosure are used for planthealth applications on cereals at a use rate that is lower than theminimum use rate of a range of use rates listed on the label of acommercially available azoxystrobin fungicide product. In someembodiments, an azoxystrobin formulation of the current disclosure isused at a rate that is less than about 75%, about 60%, about 50%, about40%, about 30%, about 20% or about 10% of the use rate (or the minimumuse rate of a range of use rates) listed on the label of a commerciallyavailable azoxystrobin fungicide product. When used for plant healthapplications, the azoxystrobin formulations of the present disclosurecan be used at active ingredient rates that correspond to any of thevalues or ranges of values noted above for the control of fungaldiseases on cereals.

Azoxystrobin—Cereals—Corn

Labelled use rates for the control of various fungal diseases of corn byQuadris, ^(a) commercially available azoxystrobin suspensionconcentrate, are provided in Table 5.

TABLE 5 Product Target Fungi Use Rate (g ai/ha) Quadris ® Rust (Pucciniasorghi) about 109-about 164 Anthracnose leaf blight (Colletotrichumgraminicola), about 109-282 Gray leaf spot (Cercospora sorghi), Northerncorn leaf blight (Setosphaeria turcica), Northern corn leaf spot(Cochliobolus carbonum), Southern corn leaf blight (Cochliobolusheterostrophus), Eye spot (Aureobasidium zeoe) Soilborne diseases:Southern blight (Sclerotium 9.7-19.3 g/1000 row rolfsii), Rhizoctoniasolani (Rhizoctonia solani) meters

In some embodiments, the azoxystrobin formulations of the presentdisclosure are used to control fungal diseases of corn (including Fieldcorn, pop corn, and sweet corn, as well as corn grown for seedproduction) at an active ingredient use rate that is lower than the userate listed on the labels of commercially available azoxystrobinfungicides. In some embodiments, an azoxystrobin formulation of thecurrent disclosure may be used to control fungal diseases of corn at ause rate that is less than 75%, less than 60%, less than 50%, less than40%, less than 30%, less than 20%, or less than 10% of a use rate listedon the label of commercially available azoxystrobin fungicides.

In some embodiments, the azoxystrobin formulations of the currentdisclosure are used to control fungal disease of corn at an activeingredient use rate that is lower than the minimum use rate of a rangeof use rates listed on the labels of commercially available azoxystrobinproducts. In some embodiments an azoxystrobin formulation of the currentdisclosure is used to control fungal disease at a use rate that is lessthan about 75%, less than about 60%, less than about 50%, less thanabout 40%, less than about 30%, less than about 20% or less than about10% of the minimum use rate of a range of use rates listed on the labelof a commercially available azoxystrobin product.

In some embodiments, the azoxystrobin formulations of the currentdisclosure may be used to control fungal diseases of corn at an activeingredient use rate of about 82-about 212 g/ha, about 65-about 169 g/ha,about 54-about 141 g/ha, about 44-about 113 g/ha, about 33-about 85g/ha, about 22-about 56 g/ha, or about 11-about 28 g/ha. In someembodiments, the azoxystrobin formulations of the current disclosure maybe used to control fungal diseases of corn at an active ingredient userate of about 82-about 123 g/ha, about 65-about 98 g/ha, about 55-about82 g/ha, about 44-about 66 g/ha, about 33-about 49 g/ha, about 22-about33 g/ha, or about 11-about 16 g/ha.

In some embodiments, the azoxystrobin formulations of the currentdisclosure may be used to control fungal diseases of corn at an activeingredient use rate of less than about 82 g/ha, less than about 65 g/ha,less than about 54 g/ha, less than about 44 g/ha, less than about 33g/ha, less than about 22 g/ha, or less than about 11 g/ha. In someembodiments, the azoxystrobin formulations of the present disclosure maybe used to control fungal diseases of corn at an active ingredient userate of less than about 82 g/ha, less than about 65 g/ha, less thanabout 55 g/ha, less than about 44 g/ha, less than about 33 g/ha, lessthan about 22 g/ha, or less than about 11 g/ha.

Non-limiting examples of fungal diseases of corn that can be controlledwith formulations of the present disclosure are Anthracnose leaf blight(Colletotrichum graminicola, Gray leaf spot (Cercospora sorghi),Northern corn leaf blight (Setosphaeria turcica), Northern corn leafspot (Cochliobolus carbonum), Southern corn leaf blight (Cochliobolusheterostrophus) and Eye spot (Aureobasidium zeae).

In some embodiments, the azoxystrobin formulations of the presentdisclosure are used to control Puccinia sorghi at an active ingredientuse rate of about 82-about 123 g/ha, about 65-about 98 g/ha, about55-about 82 g/ha, about 44-about 66 g/ha, about 33-about 49 g/ha, about22-about 33 g/ha, or about 11-about 16 g/ha.

In some embodiments, the azoxystrobin formulations of the currentdisclosure are used to control soilborne fungal diseases of corn at anactive ingredient use rate that is lower than the use rate (or lowerthan the minimum use rate of a range of use rates) listed on the labelof commercially available azoxystrobin fungicides. In some embodiments,a formulations of the current disclosure is used to control soilbornefungal diseases of corn at a use rate that is less than about 75%, lessthan about 60%, less than about 50%, less than about 40%, less thanabout 30%, less than about 20% or less than about 10% of a use ratelisted on the label of a commercially available azoxystrobin fungicideproduct. In some embodiments, an azoxystrobin formulation of the currentdisclosure is used to control soilborne fungal diseases of corn at a userate that is less than about 75%, less than about 60%, less than about50%, less than about 40%, less than about 30%, less than about 20% orless than about 10% of the minimum use rate of a range of use rateslisted on the label of a commercially available azoxystrobin fungicideproduct.

In various embodiments, the azoxystrobin formulations of the currentdisclosure may be used to control soilborne diseases of corn at activeingredient use rates of about 7.3-about 14.5 g per 1000 row meters,about 5.8-about 11.6 g per 1000 row meters, about 4.8-about 9.7 g per1000 row meters, about 3.9-about 7.7 g per 1000 row meters, about2.9-about 5.8 g per 1000 row meters, about 1.9-about 3.9 g per 1000 rowmeters or about 1.0-about 1.9 g per 1000 row meters. In someembodiments, the azoxystrobin formulations of the current disclosure maybe used to control soilborne diseases of corn at active ingredient userates of less than about 1.0 g per 1000 row meters, less than about 1.9g per 1000 row meters, less than about 2.9 g per 1000 row meters, lessthan about 3.9 g per 1000 row meters, less than about 4.8 g per 1000 rowmeters, less than about 5.8 g per 1000 row meters, less than about 7.3 gper 1000 row meters, less than about 7.7 g per 1000 row meters, lessthan about 9.7 g per 1000 row meters, less than about 11.6 g per 1000row meters or less than about 14.5 g per 1000 row meters.

Non-limiting examples of the types of soilborne diseases of corn thatcan be controlled by azoxystrobin formulations of the current disclosureare Rhizoctonia root and stalk rot (Rhizoctonia solani).

In some embodiments, the azoxystrobin formulations of the currentdisclosure are used for plant health applications on corn at a use ratethat is lower than a use rate listed on the label of a commerciallyavailable azoxystrobin fungicide product. In some embodiments, theazoxystrobin formulations of the current disclosure are used for planthealth applications on corn at a use rate that is lower than the minimumuse rate of a range of use rates listed on the label of a commerciallyavailable azoxystrobin fungicide product. In some embodiments, anazoxystrobin formulation of the current disclosure is used at a ratethat is less than about 75%, about 60%, about 50%, about 40%, about 30%,about 20% or about 10% of the use rate (or the minimum use rate of arange of use rates) listed on the label of a commercially availableazoxystrobin fungicide product. When used for plant health applications,the azoxystrobin formulations of the present disclosure can be used atactive ingredient rates that correspond to any of the values or rangesof values noted above for the control of fungal diseases on corn.

Azoxystrobin—Cereals—Wheat

Labelled use rates for the control of various fungal diseases of wheatby Amistar® and Priori®, two commercially available azoxystrobinconcentrates, are provided in Table 6.

TABLE 6 Use Rate Product Target Fungi (g ai/ha) Priori ® Bipolarissorokiniana, Drechslera tritici-repentis, 50-100 Puccinia triticinaAmistar ® Powdery mildew (Erysiphe graminis), Septoria 250 nodorum,Septoria leaf blotch (Septoria tritici), Drechslera tritici-repentis,Yellow Rust (Puccinia striiformis), Brown Rust (Puccinia recondita)

In some embodiments, the azoxystrobin formulations of the currentdisclosure are used to control fungal diseases of wheat at an activeingredient use rate that is lower than the use rate listed on the labelsof commercially available azoxystrobin fungicides. In some embodiments,a formulation of the current disclosure is used to control fungaldiseases of wheat at a use rate that is less than about 75%, less thanabout 60%, less than about 50%, less than about 40%, less than about30%, less than about 20%, or less than about 10% of a use rate listed onthe label of commercially available azoxystrobin fungicide products.

In some embodiments, the azoxystrobin formulations of the currentdisclosure are used to control fungal disease of wheat at an activeingredient use rate that is lower than the minimum use rate of a rangeof use rates listed on the label of a commercially availableazoxystrobin product. In some embodiments an azoxystrobin formulation ofthe current disclosure is used to control fungal disease at a use ratethat is less than about 75%, less than about 60%, less than about 50%,less than about 40%, less than about 30%, less than about 20% or lessthan about 10% of the minimum use rate of a range of use rates listed ona label of a commercially available azoxystrobin product.

In some embodiments, the azoxystrobin formulations of the currentdisclosure may be used to control fungal diseases of corn at an activeingredient use rate of about 37.5-about 75 g/ha, about 30-about 60 g/ha,about 25-about 50 g/ha, about 20-about 40 g/ha, about 15-about 30 g/ha,about 10-about 20 g/ha or about 5-about 10 g/ha.

In some embodiments, the azoxystrobin formulations of the currentdisclosure may be used to control fungal diseases of corn at an activeingredient use rate of less than about 37.5 g/ha, less than about 30g/ha, less than about 25 g/ha, less than about 20 g/ha, less than about15 g/ha, less than about 10 g/ha or less than about 5 g/ha.

In some embodiments, the azoxystrobin formulations of the presentdisclosure may be used to control fungal diseases of corn at an activeingredient use rate of less than about 187.5 g/ha, less than about 150g/ha, less than about 125 g/ha, less than about 100 g/ha, less thanabout 75 g/ha, less than about 50 g/ha or less than about 25 g/ha.

Non-limiting examples of fungal diseases of wheat that can be controlledwith formulations of the present disclosure are Bipolaris sorokiniana,tan spot (Drechslera tritici-repentis), and Wheat leaf rust (Pucciniatriticina), and other fungal diseases listed in table X.

In some embodiments, the azoxystrobin formulations of the presentdisclosure are used for plant health applications on corn at a use ratethat is lower than the use rate listed on the label of commerciallyavailable azoxystrobin fungicides. In some embodiment, the azoxystrobinformulations of the present disclosure are used at a rate that is 75%,60%, 50%, 40%, 30%, 20% or 10% of the use rate listed on the labels ofcommercially available azoxystrobin fungicides. When used for planthealth applications, the azoxystrobin formulations of the presentdisclosure can be used at an active ingredient use rate that correspondsto any of the values or ranges of values noted above for the control offungal diseases on corn.

In some embodiments, the azoxystrobin formulations of the currentdisclosure are used for plant health applications on wheat at a use ratethat is lower than a use rate listed on the label of a commerciallyavailable azoxystrobin fungicide product. In some embodiments, theazoxystrobin formulations of the current disclosure are used for planthealth applications on wheat at a use rate that is lower than theminimum use rate of a range of use rates listed on the label of acommercially available azoxystrobin fungicide product. In someembodiments, an azoxystrobin formulation of the current disclosure isused at a rate that is less than about 75%, about 60%, about 50%, about40%, about 30%, about 20% or about 10% of the use rate (or the minimumuse rate of a range of use rates) listed on the label of a commerciallyavailable azoxystrobin fungicide product. When used for plant healthapplications, the azoxystrobin formulations of the present disclosurecan be used at active ingredient rates that correspond to any of thevalues or ranges of values noted above for the control of fungaldiseases on wheat.

Azoxystrobin—Cereals—Rice

Labelled use rates for the control of various fungal diseases of rice byQuadris® and Priori®, two commercially available azoxystrobinconcentrates, are provided in Table 7.

TABLE 7 Product Target Fungi Use Rate (g ai/ha) Quadris ® Sheath blight(Rhizoctonia solani) 164-228 Aggregate sheath spot (Ceratobasidiumoryzae-sativae = 228-282 Rhizoctonia oryzae-sativae), Black sheath rot(Gaeumannomyces graminis var. graminis), Sheath spot (Rhizoctoniaoryzae), Stem rot (Magnaporthe salvinii = Sclerotium oryzae = Nakateaesigmoidea), Brown leaf spot (Cochliobolus miyabeanus), Leaf smut(Entyloma oryzae), Narrow brown leaf spot (Cercospora janseana =Cercospora oryzae), Kernel smut (Tilletia barclayana = Neovossiabarclayana), Panicle blast (Pyricularia grisea) Priori ® Bipolarisoryzae, Pyricularia grisea 100

In some embodiments, the azoxystrobin formulations of the currentdisclosure are used to control fungal diseases of rice at an activeingredient use rate that is lower than the use rate listed on the labelsof commercially available azoxystrobin fungicides. In some embodiments,a formulation of the current disclosure is used to control fungaldiseases of rice at a use rate that is less than about 75%, less thanabout 60%, less than about 50%, less than about 40%, less than about30%, less than about 20%, or less than about 10% of a use rate listed onthe label of commercially available azoxystrobin fungicide products.

In some embodiments, the azoxystrobin formulations of the currentdisclosure are used to control fungal disease of rice at an activeingredient use rate that is lower than the minimum use rate of a rangeof use rates listed on the label of a commercially availableazoxystrobin product. In some embodiments an azoxystrobin formulation ofthe current disclosure is used to control fungal disease at a use ratethat is less than about 75%, less than about 60%, less than about 50%,less than about 40%, less than about 30%, less than about 20% or lessthan about 10% of the minimum use rate of a range of use rates listed onthe label of a commercially available azoxystrobin product.

In some embodiments, the azoxystrobin formulations of the currentdisclosure are used to control fungal diseases of rice at an activeingredient use rate of about 171-about 212 g/ha, about 137-about 169g/ha, about 114-about 141 g/ha, about 91-about 113 g/ha, about 68-about85 g/ha, about 46-about 56 g/ha or about 23-about 28 g/ha. In someembodiments, the azoxystrobin formulations of the present disclosure areused to control fungal diseases of rice at an active ingredient use rateof about 123-about 171 g/ha, about 98-about 137 g/ha, about 82-about 114g/ha, about 66-about 91 g/ha, about 49-about 68 g/ha, about 33-about 46g/ha or about 16-about 23 g/ha.

In some embodiments, the azoxystrobin formulations of the currentdisclosure are used to control fungal diseases of rice at an activeingredient use rate of less than about 171 g/ha, less than about 137g/ha, less than about 114 g/ha, less than about 91 g/ha, less than about68 g/ha, less than about 46 g/ha or less than about 23 g/ha. In someembodiments, the azoxystrobin formulations of the present disclosure areused to control fungal diseases of rice at an active ingredient use rateof less than about 123 g/ha, less than about 98 g/ha, less than about 82g/ha, less than about 66 g/ha, less than about 49 g/ha, less than about33 g/ha or less than about 16 g/ha.

In some embodiments, the azoxystrobin formulations of the presentdisclosure are used to control fungal diseases of rice at an activeingredient use rate of about 123-about 171 g/ha, about 98-about 137g/ha, about 82-about 114 g/ha, about 66-about 91 g/ha, about 49-about 68g/ha, about 33-about 46 g/ha or about 16-about 23 g/ha.

In some embodiments, the azoxystrobin formulations of the presentdisclosure are used to control fungal diseases of rice at an activeingredient use rate of less than about 123 g/ha, less than about 98g/ha, less than about 82 g/ha, less than about 66 g/ha, less than about49 g/ha, less than about 33 g/ha or less than about 16 g/ha.

In some embodiments, the azoxystrobin formulations of the currentdisclosure may be used to control fungal diseases of rice at an activeingredient use rates of less than about 75 g/ha, less than about 60g/ha, less than about 50 g/ha, less than about 40 g/ha, less than about30 g/ha, less than about 20 g/ha or less than about 10 g/ha.

Non-limiting examples of fungal diseases of rice that can be controlledwith formulations of the present disclosure are Aggregate sheath spot(Ceratobasidium oryzae-sativae=Rhizoctonia oryzae-sativae), Black sheathrot (Gaeumannomyces graminis var. graminis), Sheath spot (Rhizoctoniaoryzae), Stem rot (Magnaporthe salvia=Sclerotium oryzae=Nakateaesigmoidea), Brown leaf spot (Cochliobolus miyabeanus), Leaf smut(Entyloma oryzae), Narrow brown leaf spot (Cercosporajanseana=Cercospora oryzae), Kernel smut (Tilletia barclayana=Neovossiabarclayana) Panicle blast (Pyricularia grisea) and Bipolaris oryzae.

In some embodiments, the azoxystrobin formulations of the currentdisclosure are used for plant health applications on rice at a use ratethat is lower than a use rate listed on the label of a commerciallyavailable azoxystrobin fungicide product. In some embodiments, theazoxystrobin formulations of the current disclosure are used for planthealth applications on rice at a use rate that is lower than the minimumuse rate of a range of use rates listed on the label of a commerciallyavailable azoxystrobin fungicide product. In some embodiments, anazoxystrobin formulation of the current disclosure is used at a ratethat is less than about 75%, about 60%, about 50%, about 40%, about 30%,about 20% or about 10% of the use rate (or the minimum use rate of arange of use rates) listed on the label of a commercially availableazoxystrobin fungicide product. When used for plant health applications,the azoxystrobin formulations of the present disclosure can be used atactive ingredient rates that correspond to any of the values or rangesof values noted above for the control of fungal diseases on rice.

Azoxystrobin—Potatoes

Labelled use rates for the control of various fungal diseases ofpotatoes by Quadris®, a commercially available azoxystrobin suspensionconcentrate, are provided in Table 8.

TABLE 8 Product Target Fungi Use Rate (g ai/ha) Quadris ® Early blight(Alternaria solani), Late blight 109-282 (Phytophthora infestans), Blackdot (Colletotrichum coccodes), Powdery mildew (Erysiphe cichoracearum)Soilborne Diseases 9.7-19.3 g/1000 row Black scurf (Rhizoctonia solani),Silver scurf meters (Helminthosporium solani), Black dot (Colletotrichumcoccodes)

In some embodiments, the azoxystrobin formulations of the currentdisclosure are used to control fungal diseases of potatoes at an activeingredient use rate that is lower than the use rate listed on the labelsof commercially available azoxystrobin fungicides. In some embodiments,a formulation of the current disclosure is used to control fungaldiseases of potatoes at a use rate that is less than about 75%, lessthan about 60%, less than about 50%, less than about 40%, less thanabout 30%, less than about 20%, or less than about 10% of a use ratelisted on the label of commercially available azoxystrobin fungicideproducts.

In some embodiments, the azoxystrobin formulations of the currentdisclosure are used to control fungal disease of potatoes at an activeingredient use rate that is lower than the minimum use rate of a rangeof use rates listed on the label of a commercially availableazoxystrobin product. In some embodiments an azoxystrobin formulation ofthe current disclosure is used to control fungal disease at a use ratethat is less than about 75%, less than about 60%, less than about 50%,less than about 40%, less than about 30%, less than about 20% or lessthan about 10% of the minimum use rate of a range of use rates listed onthe label of a commercially available azoxystrobin product.

In some embodiments, the azoxystrobin formulations of the presentdisclosure are used to control fungal diseases of potatoes at an activeingredient use rate of about 82-about 212 g/ha, about 66-about 169 g/ha,about 55-about 141 g/ha, about 44-about 113 g/ha, about 33-about 85g/ha, about 22-about 56 g/ha or about 11-about 28 g/ha.

In some embodiments, the azoxystrobin formulations of the presentdisclosure are used to control fungal diseases of potatoes at an activeingredient use rate of less than about 82 g/ha, less than about 66 g/ha,less than about 55 g/ha, less than about 44 g/ha, less than about 33g/ha, less than about 22 g/ha or less than about 11 g/ha.

Non-limiting examples of fungal diseases of potatoes that can becontrolled with formulations of the present disclosure are Early blight(Alternaria solani), Late blight (Phytophthora infestans), Black dot(Colletotrichurn coccodes) and Powdery mildew (Erysiphe cichoracearum).

In some embodiments, the azoxystrobin formulations of the presentdisclosure may be used to control soilborne fungal diseases of potatoesat an active ingredient use rate that is lower than the use rate (orminimum rate of a range of use rates) listed on the label of acommercially available azoxystrobin fungicide product. In someembodiments, the formulations of the current disclosure are used tocontrol soilborne fungal diseases of potatoes at a use rate that is lessthan about 75%, about 60%, about 50%, about 40%, about 30%, about 20% orabout 10% of the use rate (or minimum use rate of a range of use rates)listed on the label of a commercially available azoxystrobin fungicideproduct.

In various embodiments, the azoxystrobin formulations of the currentdisclosure may be used to control soilborne diseases of potatoes atactive ingredient use rates of about 7.3-about 14.5 g per 1000 rowmeters, about 5.8-about 11.6 g per 1000 row meters, about 4.8-about 9.7g per 1000 row meters, about 3.9-about 7.7 g per 1000 row meters, about2.9-about 5.8 g per 1000 row meters, about 1.9-about 3.9 g per 1000 rowmeters or about 1.0-about 1.9 g per 1000 row meters. In variousembodiments, the azoxystrobin formulations of the current disclosure maybe used to control soilborne diseases of potatoes at active ingredientuse rates of less than about 7.3 g per 1000 row meters, less than about5.8 g per 1000 row meters, less than about 4.8 g per 1000 row meters,less than about 3.9 g per 1000 row meters, less than about 2.9 g per1000 row meters, less than about 1.9 g per 1000 row meters or less thanabout 1.0 g per 1000 row meters.

Non-limiting examples of the types of soilborne diseases of potatoesthat can be controlled by azoxystrobin formulations of the presentdisclosure are Black scurf (Rhizoctonia solani), Silver scurf(Helminthosporium solani), Black dot (Colletotrichum coccodes).

In some embodiments, the azoxystrobin formulations of the currentdisclosure are used for plant health applications on potatoes at a userate that is lower than a use rate listed on the label of a commerciallyavailable azoxystrobin fungicide product. In some embodiments, theazoxystrobin formulations of the current disclosure are used for planthealth applications on potatoes at a use rate that is lower than theminimum use rate of a range of use rates listed on the label of acommercially available azoxystrobin fungicide product. In someembodiments, an azoxystrobin formulation of the current disclosure isused at a rate that is less than about 75%, about 60%, about 50%, about40%, about 30%, about 20% or about 10% of the use rate (or the minimumuse rate of a range of use rates) listed on the label of a commerciallyavailable azoxystrobin fungicide product. When used for plant healthapplications, the azoxystrobin formulations of the present disclosurecan be used at active ingredient rates that correspond to any of thevalues or ranges of values noted above for the control of fungaldiseases on potatoes.

Azoxystrobin—Turf, Ornamental and Other Applications

In some embodiments, the azoxystrobin formulations of the presentdisclosure are used to control fungal diseases of turf, ornamental, andlandscape plants, sod and turf grasses grown for seed. In someembodiments, the formulations of the present disclosure are used tocontrol fungal disease of the aforementioned plants at an activeingredient use rate that is lower than the use rate listed on the labelof commercially available azoxystrobin fungicides. In some embodiments,the formulations of the current disclosure are used to control fungaldiseases of turf, ornamental and landscape plants at a use rate that isless than about 75%, about 60%, about 50%, about 40%, about 30%, about20%, or about 10% of the use rate listed on commercially availableazoxystrobin fungicides.

In some embodiments, the azoxystrobin formulations of the currentdisclosure are used to control fungal disease of turf, ornamental, andlandscape plants, sod and turf grasses grown for seed at an activeingredient use rate that is lower than the minimum use rate of a rangeof use rates listed on the label of a commercially availableazoxystrobin product. In some embodiments an azoxystrobin formulation ofthe current disclosure is used to control fungal disease of theaforementioned plants at a use rate that is less than about 75%, lessthan about 60%, less than about 50%, less than about 40%, less thanabout 30%, less than about 20% or less than about 10% of the minimum userate of a range of use rates listed on the label of a commerciallyavailable azoxystrobin product.

Examples of the aforementioned plants on which fungal disease can becontrolled by formulations of the present disclosure can be found on thelabels of commercially available azoxystrobin fungicides (e.g.,Heritage® etc.).

In some embodiments, the azoxystrobin formulations of the presentdisclosure are used for plant health applications on the aforementionedplants at a use rate that is lower than the use rate (or minimum userate of a range of use rates) listed on the label of a commerciallyavailable azoxystrobin fungicide product (e.g., Heritage®). In someembodiments, the azoxystrobin formulations of the current disclosure areused at a rate that is less than about 75%, about 60%, about 50%, about40%, about 30%, about 20% or about 10% of the use rate (or minimum userate of a range of use rates) listed on the label of a commerciallyavailable azoxystrobin fungicide product. When used for plant healthapplications, the azoxystrobin formulations of the current disclosurecan be used at active ingredient rates that correspond to any of thevalues or ranges of values noted above for the control of fungaldiseases on turf, ornamental, and landscape plants, sod and turf grassesgrown for seed.

Pyraclostrobin

In various embodiments, the pyraclostrobin formulations of the currentdisclosure may be used to control fungal diseases at active ingredientuse rates that are lower than the use rates listed on the labels ofcommercially available pyraclostrobin fungicides. In some embodiments, apyraclostrobin formulation of the current disclosure may be used tocontrol fungal disease at a use rate that is less than about 75%, lessthan about 60%, less than about 50%, less than about 40%, less thanabout 30%, less than about 20% or less than about 10% of a use ratelisted on the label of a commercially available pyraclostrobin fungicideproduct.

Labels of commercially available pyraclostrobin products often provideranges of active ingredient use rates to control certain fungal diseaseson certain plants (e.g., crops). In some embodiments, the pyraclostrobinformulations of the current disclosure are used to control fungaldisease at an active ingredient use rate that is lower than the minimumuse rate of a range of use rates listed on the label of a commerciallyavailable pyraclostrobin product. In some embodiments a pyraclostrobinformulation of the current disclosure is used to control fungal diseaseat a use rate that is less than about 75%, less than about 60%, lessthan about 50%, less than about 40%, less than about 30%, less thanabout 20% or less than about 10% of the minimum use rate of a range ofuse rates listed on the label of a commercially available product.

Pyraclostrobin—Cereals

In some embodiments, the pyraclostrobin formulations of the currentdisclosure are used to control fungal diseases of cereals at an activeingredient use rate that is lower than the use rate listed on the labelsof commercially available pyraclostrobin fungicides. In someembodiments, a formulation of the current disclosure is used to controlfungal diseases of cereals at a use rate that is less than about 75%,less than about 60%, less than about 50%, less than about 40%, less thanabout 30%, less than about 20%, or less than about 10% of a use ratelisted on the label of commercially available pyraclostrobin fungicideproducts.

In some embodiments, the pyraclostrobin formulations of the currentdisclosure are used to control fungal disease of cereals at an activeingredient use rate that is lower than the minimum use rate of a rangeof use rates listed on the label of a commercially availablepyraclostrobin product. In some embodiments an pyraclostrobinformulation of the current disclosure is used to control fungal diseaseat a use rate that is less than about 75%, less than about 60%, lessthan about 50%, less than about 40%, less than about 30%, less thanabout 20% or less than about 10% of the minimum use rate of a range ofuse rates listed on the label of a commercially available pyraclostrobinproduct.

Examples of fungal diseases of cereals and corresponding activeingredient use rates for their control can be found on the labels ofcommercially available pyraclostrobin fungicide products (e.g.,Headline®). Examples of fungal diseases of cereals that can becontrolled with formulations of the present disclosure include but arenot limited to various blights, spots and rusts, rots, blasts and smuts.

In some embodiments, the pyraclostrobin formulations of the currentdisclosure are used for plant health applications on cereals at a userate that is lower than a use rate listed on the label of a commerciallyavailable pyraclostrobin fungicide product. In some embodiments, thepyraclostrobin formulations of the current disclosure are used for planthealth applications on cereals at a use rate that is lower than theminimum use rate of a range of use rates listed on the label ofcommercially available pyraclostrobin fungicide product. In someembodiments, a pyraclostrobin formulation of the current disclosure isused at a rate that is less than about 75%, about 60%, about 50%, about40%, about 30%, about 20% or about 10% of the use rate (or the minimumuse rate of a range of use rates) listed on the label of a commerciallyavailable pyraclostrobin fungicide product. When used for plant healthapplications, the pyraclostrobin formulations of the present disclosurecan be used at active ingredient rates that correspond to any of thevalues or ranges of values noted above for the control of fungaldiseases on cereals.

Pyraclostrobin—Cereals—Wheat

Labelled use rates for the control of various fungal diseases of wheatby Headline®, Comet® and Comet 200®, three commercially availablepyraclostrobin emulsion concentrates, are provided in Table 9.

TABLE 9 Product Target Fungi Use Rate (g ai/ha) Headline ® Black Spot,Leaf Rust, Powdery Mildew, Septoria Leaf 110-165 And Glume Blotch, SpotBlotch, Stem Rust, Stripe Rust, Tan Spot (Yellow Leaf Spot) Comet ®Drecheslera tritici-repentis, Pucciniatriticina, Bipolaris 150-200sorokiniana, Leptosphaeria nodorum, Septoria tritici Comet Septoriatritici, Septoria nodorum, Yellow rust, brown 250 200 ® rust

In some embodiments, the pyraclostrobin formulations of the currentdisclosure are used to control fungal diseases of wheat at an activeingredient use rate that is lower than the use rate listed on the labelsof commercially available pyraclostrobin fungicides. In someembodiments, a pyraclostrobin formulation of the current disclosure isused to control fungal diseases of wheat at a use rate that is less thanabout 75%, less than about 60%, less than about 50%, less than about40%, less than about 30%, less than about 20%, or less than about 10% ofa use rate listed on the label of a commercially availablepyraclostrobin fungicide product.

In some embodiments, the pyraclostrobin formulations of the currentdisclosure are used to control fungal disease of wheat at an activeingredient use rate that is lower than the minimum use rate of a rangeof use rates listed on the label of a commercially availablepyraclostrobin product. In some embodiments a pyraclostrobin formulationof the current disclosure is used to control fungal disease at a userate that is less than about 75%, less than about 60%, less than about50%, less than about 40%, less than about 30%, less than about 20% orless than about 10% of the minimum use rate of a range of use rateslisted on the label of a commercially available pyraclostrobin product.

In some embodiments, the pyraclostrobin formulations of the presentdisclosure are used to control fungal diseases of wheat at an activeingredient use rate of about 82-about 124 g/ha, about 66-about 99 g/ha,about 55-about 82 g/ha, about 44-about 66 g/ha, about 33-about 49 g/ha,about 22-about 33 g/ha or about 11-about 16 g/ha. In some embodiments,the pyraclostrobin formulations of the present disclosure are used tocontrol fungal diseases of wheat at an active ingredient use rate ofabout 112.5-about 150 g/ha, about 90-about 120 g/ha, about 75-about 100g/ha, about 60-about 80 g/ha, about 45-about 60 g/ha, about 30-about 40g/ha or about 15-about 20 g/ha.

In some embodiments, the pyraclostrobin formulations of the presentdisclosure are used to control fungal diseases of wheat at an activeingredient use rate of less than about 82 g/ha, less than about 66 g/ha,less than about 55 g/ha, less than about 44 g/ha, less than about 33g/ha, less than about 22 g/ha or less than about 11 g/ha. In someembodiments, the pyraclostrobin formulations of the present disclosureare used to control fungal diseases of wheat at an active ingredient userate of less than about 112.5 150 g/ha, less than about 90 g/ha, lessthan about 75 g/ha, less than about 60 g/ha, less than about 45 g/ha,less than about 30 g/ha or less than about 15 g/ha.

In some embodiments, the pyraclostrobin formulations of the currentdisclosure can be used to control fungal diseases of wheat at an activeingredient use rates of about less than about 187.5 g/ha, less thanabout 150 g/ha, less than about 125 g/ha, less than about 100 g/ha, lessthan about 75 g/ha, less than about 50 g/ha, or less than about 25 g/ha.

Non-limiting examples of fungal diseases of wheat that can be controlledwith formulations of the present disclosure include those listed inTable 9, above.

In some embodiments, the pyraclostrobin formulations of the currentdisclosure are used for plant health applications on wheat at a use ratethat is lower than a use rate listed on the label of a commerciallyavailable pyraclostrobin fungicide product. In some embodiments, thepyraclostrobin formulations of the current disclosure are used for planthealth applications on wheat at a use rate that is lower than theminimum use rate of a range of use rates listed on the label of acommercially available pyraclostrobin fungicide product. In someembodiments, a pyraclostrobin formulation of the current disclosure isused at a rate that is less than about 75%, about 60%, about 50%, about40%, about 30%, about 20% or about 10% of the use rate (or the minimumuse rate of a range of use rates) listed on the label of a commerciallyavailable pyraclostrobin fungicide product. When used for plant healthapplications, the pyraclostrobin formulations of the present disclosurecan be used at active ingredient rates that correspond to any of thevalues or ranges of values noted above for the control of fungaldiseases on wheat.

Pyraclostrobin—Cereals—Corn

Labelled use rates for the control of various fungal diseases of corn byHeadline®, Comet® and Comet 200®, there commercially availablepyraclostrobin emulsion concentrates, are provided in Table 10.

TABLE 10 Use Rate Product Target Fungi (g ai/ha) Headline ® On corn (alltypes, including field, sweet, pop, 110-220 field corn, and corn grownfor seed production): Anthracnose, Gray Leaf Spot, Northern Corn LeafBlight, Physoderma Brown Spot, Common Rust, Southern Rust, Southern CornLeaf Blight, Yellow Leaf Blight Comet ® Puccinia polysora, Phaeosphaeriamaydis 150

In some embodiments, the pyraclostrobin formulations of the currentdisclosure are used to control fungal diseases of corn at an activeingredient use rate that is lower than the use rate listed on the labelsof commercially available pyraclostrobin fungicides. In someembodiments, a pyraclostrobin formulation of the current disclosure isused to control fungal diseases of corn at a use rate that is less thanabout 75%, less than about 60%, less than about 50%, less than about40%, less than about 30%, less than about 20%, or less than about 10% ofa use rate listed on the label of a commercially availablepyraclostrobin fungicide product.

In some embodiments, the pyraclostrobin formulations of the currentdisclosure are used to control fungal disease of corn at an activeingredient use rate that is lower than the minimum use rate of a rangeof use rates listed on the label of a commercially availablepyraclostrobin product. In some embodiments a pyraclostrobin formulationof the current disclosure is used to control fungal disease at a userate that is less than about 75%, less than about 60%, less than about50%, less than about 40%, less than about 30%, less than about 20% orless than about 10% of the minimum use rate of a range of use rateslisted on the label of a commercially available pyraclostrobin product.

In some embodiments, the pyraclostrobin formulations of the presentdisclosure are used to control fungal diseases of corn at an activeingredient use rate of about 82-about 165 g/ha, about 66-about 132 g/ha,about 55-about 110 g/ha, about 44-about 88 g/ha, about 33-about 66 g/ha,about 22-about 44 g/ha or about 11-about 22 g/ha.

In some embodiments, the pyraclostrobin formulations of the presentdisclosure are used to control fungal diseases of corn at an activeingredient use rate of less than about 82 g/ha, less than about 66 g/ha,less than about 55 g/ha, less than about 44 g/ha, less than about 33g/ha, less than about 22 44 g/ha or less than about 11 g/ha.

In some embodiments, the pyraclostrobin formulations of the currentdisclosure can be used to control fungal diseases of corn at an activeingredient use rates of less than about 112.5 g/ha, less than about 90g/ha, less than about 75 g/ha, less than about 60 g/ha, less than about45 g/ha, less than about 30 g/ha, or less than about 15 g/ha.

Non-limiting examples of fungal diseases of corn that can be controlledwith pyraclostrobin formulations of the present disclosure include thoselisted in Table 10, above.

In some embodiments, the pyraclostrobin formulations of the currentdisclosure are used for plant health applications on corn at a use ratethat is lower than a use rate listed on the label of a commerciallyavailable pyraclostrobin fungicide product. In some embodiments, thepyraclostrobin formulations of the current disclosure are used for planthealth applications on corn at a use rate that is lower than the minimumuse rate of a range of use rates listed on the label of a commerciallyavailable pyraclostrobin fungicide product. In some embodiments, apyraclostrobin formulation of the current disclosure is used at a ratethat is less than about 75%, about 60%, about 50%, about 40%, about 30%,about 20% or about 10% of the use rate (or the minimum use rate of arange of use rates) listed on the label of a commercially availablepyraclostrobin fungicide product. When used for plant healthapplications, the pyraclostrobin formulations of the present disclosurecan be used at active ingredient rates that correspond to any of thevalues or ranges of values noted above for the control of fungaldiseases on corn.

Pyraclostrobin—Soybean

Labelled use rates for the control of various fungal diseases of soybeanby Headline®, and Comet®, two commercially available pyraclostrobinemulsion concentrates, are provided in Table 11.

TABLE 11 Use Rate Product Target Fungi (g ai/ha) Headline ® AlternariaLeaf Spot, Anthracnose, Asian 110-220 Soybean Rust, Brown Spot,Cercospora Blight, Frogeye Leaf Spot, Pod and Stem Blight, RhizoctoniaAerial Blight Suppression only: Southern blight 220 Comet ® Mycrosphaeradiffusa, Cercospora kikuchii,  75 Septoria glycines, Corynesporacassiicola

In some embodiments, the pyraclostrobin formulations of the currentdisclosure are used to control fungal diseases of soybean at an activeingredient use rate that is lower than the use rate listed on the labelsof commercially available pyraclostrobin fungicides. In someembodiments, a pyraclostrobin formulation of the current disclosure isused to control fungal diseases of soybean at a use rate that is lessthan about 75%, less than about 60%, less than about 50%, less thanabout 40%, less than about 30%, less than about 20%, or less than about10% of a use rate listed on the label of a commercially availablepyraclostrobin fungicide product.

In some embodiments, the pyraclostrobin formulations of the currentdisclosure are used to control fungal disease of soybean at an activeingredient use rate that is lower than the minimum use rate of a rangeof use rates listed on the label of a commercially availablepyraclostrobin product. In some embodiments a pyraclostrobin formulationof the current disclosure is used to control fungal disease at a userate that is less than about 75%, less than about 60%, less than about50%, less than about 40%, less than about 30%, less than about 20% orless than about 10% of the minimum use rate of a range of use rateslisted on the label of a commercially available pyraclostrobin product.

In some embodiments, the pyraclostrobin formulations of the presentdisclosure are used to control fungal diseases of soybean at an activeingredient use rate of about 82-about 165 g/ha, about 66-about 132 g/ha,about 55-about 110 g/ha, about 44-about 88 g/ha, about 33-about 66 g/ha,about 22-about 44 g/ha or about 11-about 22 g/ha.

In some embodiments, the pyraclostrobin formulations of the presentdisclosure are used to control fungal diseases of soybean at an activeingredient use rate of less than about 82 g/ha, less than about 66 g/ha,less than about 55 g/ha, less than about 44 g/ha, less than about 33g/ha, less than about 22 g/ha or less than about 11 g/ha.

In some embodiments, the pyraclostrobin formulations of the presentdisclosure can be used to control fungal diseases of soybean at anactive ingredient use rate of less than about 165 g/ha, less than about131 g/ha, less than about 110 g/ha, less than about 88 g/ha, less thanabout 66 g/ha, less than about 44 g/ha, or less than about 22 g/ha. Insome embodiments, the pyraclostrobin formulations of the currentdisclosure can be used to control fungal diseases of soybean at anactive ingredient use rate of less than about 56 g/ha, less than about45 g/ha, less than about 37.5 g/ha, less than about 30 g/ha, less thanabout 22.5 g/ha, less than about 15 g/ha, or less than about 7.5 g/ha.

Non-limiting examples of fungal diseases of soybeans that can becontrolled with formulations of the present disclosure include thoselisted in Table 11, above.

In some embodiments, the pyraclostrobin formulations of the currentdisclosure are used for plant health applications on soybean at a userate that is lower than a use rate listed on the label of a commerciallyavailable pyraclostrobin fungicide product. In some embodiments, thepyraclostrobin formulations of the current disclosure are used for planthealth applications on soybean at a use rate that is lower than theminimum use rate of a range of use rates listed on the label of acommercially available pyraclostrobin fungicide product. In someembodiments, a pyraclostrobin formulation of the current disclosure isused at a rate that is less than about 75%, about 60%, about 50%, about40%, about 30%, about 20% or about 10% of the use rate (or the minimumuse rate of a range of use rates) listed on the label of a commerciallyavailable pyraclostrobin fungicide product. When used for plant healthapplications, the pyraclostrobin formulations of the present disclosurecan be used at active ingredient rates that correspond to any of thevalues or ranges of values noted above for the control of fungaldiseases on soybean.

Pyraclostrobin—Cucurbits

Labelled use rates for the control of various fungal diseases ofCucurbits (vine crops) by Cabrio® and Comet®, a commercially availablepyraclostrobin water-dispersible granule, are provided in Table 12.

TABLE 12 Product Cucurbit Vegetables Labelled Target Fungi Use Rate (gai/ha) Cabrio ® Cantaloupe, Chayote, Chinese Downey mildew 112-168 EGWaxgourd, Citron Melon, Cucumber, Edible Gourds, Gherkin, Muskmelon,Pumpkin, Summer Squash, Watermelon, Winter Squash, Zucchini, MormordicaSpp. (Such As Balsam Pear, Balsam Apple, Bitter Melon, Chinese Cucumber)Alternaria Blight,  68-224 Anthracnose, Cercospora Leaf Spot, Gummy StemBlight, Plectosporium Blight, Powdery Mildew, Target Leaf Blight Comet ®Melon, watermelon Sphaerotheca fuliginea, 100 Pseudoperonospora cubensis

In some embodiments, the pyraclostrobin formulations of the currentdisclosure are used to control fungal diseases of Cucurbits at an activeingredient use rate that is lower than the use rate listed on the labelsof commercially available pyraclostrobin fungicides. In someembodiments, a pyraclostrobin formulation of the current disclosure isused to control fungal diseases of Cucurbits at a use rate that is lessthan about 75%, less than about 60%, less than about 50%, less thanabout 40%, less than about 30%, less than about 20%, or less than about10% of a use rate listed on the label of a commercially availablepyraclostrobin fungicide product.

In some embodiments, the pyraclostrobin formulations of the currentdisclosure are used to control fungal disease of Cucurbits at an activeingredient use rate that is lower than the minimum use rate of a rangeof use rates listed on the label of a commercially availablepyraclostrobin product. In some embodiments a pyraclostrobin formulationof the current disclosure is used to control fungal disease at a userate that is less than about 75%, less than about 60%, less than about50%, less than about 40%, less than about 30%, less than about 20% orless than about 10% of the minimum use rate of a range of use rateslisted on the label of a commercially available pyraclostrobin product.

In some embodiments, the pyraclostrobin formulations of the presentdisclosure may be used to control fungal diseases of Cucurbits at anactive ingredient use rate of about 84-about 126 g/ha, about 67-about101 g/ha, about 56-about 84 g/ha, about 45-about 67 g/ha, about 34-about50 g/ha, about 22-about 34 g/ha or about 11-about 17 g/ha. In someembodiments, the pyraclostrobin formulations of the present disclosuremay be used to control fungal diseases of Cucurbits at an activeingredient use rate of about 126-about 168 g/ha, about 101-about 135g/ha, about 84-about 112 g/ha, about 67-about 90 g/ha, about 50-about 67g/ha, about 34-about 45 g/ha or about 17-about 22 g/ha.

In some embodiments, the pyraclostrobin formulations of the presentdisclosure may be used to control fungal diseases of Cucurbits at anactive ingredient use rate of less than about 84 g/ha, less than about67 g/ha, less than about 56 g/ha, less than about 45 g/ha, less thanabout 34 g/ha, less than about 22 g/ha or less than about 11 g/ha. Insome embodiments, the pyraclostrobin formulations of the presentdisclosure may be used to control fungal diseases of Cucurbits at anactive ingredient use rate of less than about 126 g/ha, less than about101 g/ha, less than about 84 g/ha, less than about 67 90 g/ha, less thanabout 50 g/ha, less than about 34 g/ha or less than about 17 g/ha.

In some embodiments, the pyraclostrobin formulations of the currentdisclosure can be used to control fungal diseases of Cucurbits at anactive ingredient use rate of less than about 112.5 g/ha, less thanabout 90 g/ha, less than about 75 g/ha, less than about 60 g/ha, lessthan about 45 g/ha, less than about 30 g/ha, or less than about 15 g/ha.

Non-limiting examples of fungal diseases of Cucurbits that can becontrolled with formulations of the present disclosure include thoselisted in Table 12, above.

In some embodiments, the pyraclostrobin formulations of the currentdisclosure are used for plant health applications on Cucurbits at a userate that is lower than a use rate listed on the label of a commerciallyavailable pyraclostrobin fungicide product. In some embodiments, thepyraclostrobin formulations of the current disclosure are used for planthealth applications on Cucurbits at a use rate that is lower than theminimum use rate of a range of use rates listed on the label of acommercially available pyraclostrobin fungicide product. In someembodiments, a pyraclostrobin formulation of the current disclosure isused at a rate that is less than about 75%, about 60%, about 50%, about40%, about 30%, about 20% or about 10% of the use rate (or the minimumuse rate of a range of use rates) listed on the label of a commerciallyavailable pyraclostrobin fungicide product. When used for plant healthapplications, the pyraclostrobin formulations of the present disclosurecan be used at active ingredient rates that correspond to any of thevalues or ranges of values noted above for the control of fungaldiseases on Cucurbits.

Trifloxystrobin

In various embodiments, the trifloxystrobin formulations of the currentdisclosure may be used to control fungal diseases at active ingredientuse rates that are lower than the use rates listed on the labels ofcommercially available trifloxystrobin fungicides. In some embodiments,a trifloxystrobin formulation of the current disclosure may be used tocontrol fungal disease at a use rate that is less than about 75%, lessthan about 60%, less than about 50%, less than about 40%, less thanabout 30%, less than about 20% or less than about 10% of a use ratelisted on the label of a commercially available trifloxystrobinfungicide product.

Labels of commercially available trifloxystrobin products often provideranges of active ingredient use rates to control certain fungal diseaseson certain plants (e.g., crops). In some embodiments, thetrifloxystrobin formulations of the current disclosure are used tocontrol fungal disease at an active ingredient use rate that is lowerthan the minimum use rate of a range of use rates listed on the label ofa commercially available trifloxystrobin product. In some embodiments atrifloxystrobin formulation of the current disclosure is used to controlfungal disease at a use rate that is less than about 75%, less thanabout 60%, less than about 50%, less than about 40%, less than about30%, less than about 20% or less than about 10% of the minimum use rateof a range of use rates listed on the label of a commercially availableproduct.

Trifloxystrobin—Cereals

In some embodiments, the trifloxystrobin formulations of the currentdisclosure are used to control fungal diseases of cereals at an activeingredient use rate that is lower than the use rate listed on the labelsof commercially available azoxystrobin fungicides. In some embodiments,a trifloxystrobin formulation of the current disclosure is used tocontrol fungal diseases of cereals at a use rate that is less than about75%, less than about 60%, less than about 50%, less than about 40%, lessthan about 30%, less than about 20%, or less than about 10% of a userate listed on the label of a commercially available trifloxystrobinfungicide product.

In some embodiments, the trifloxystrobin formulations of the currentdisclosure are used to control fungal disease of cereals at an activeingredient use rate that is lower than the minimum use rate of a rangeof use rates listed on the label of a commercially availabletrifloxystrobin product. In some embodiments a trifloxystrobinformulation of the current disclosure is used to control fungal diseaseat a use rate that is less than about 75%, less than about 60%, lessthan about 50%, less than about 40%, less than about 30%, less thanabout 20% or less than about 10% of the minimum use rate of a range ofuse rates listed on the label of a commercially availabletrifloxystrobin product.

Examples of fungal diseases of cereals and corresponding activeingredient use rates for their control can be found on the labels ofcommercially available trifloxystrobin fungicide products. Examples offungal diseases of cereals that can be controlled with formulations ofthe present disclosure include but are not limited to various fungaldiseases of cereal noted in other portions of the specification.

In some embodiments, the trifloxystrobin formulations of the currentdisclosure are used for plant health applications on Cereals at a userate that is lower than a use rate listed on the label of a commerciallyavailable trifloxystrobin fungicide product. In some embodiments, thetrifloxystrobin formulations of the current disclosure are used forplant health applications on Cereals at a use rate that is lower thanthe minimum use rate of a range of use rates listed on the label ofcommercially available trifloxystrobin fungicide product. In someembodiments, a trifloxystrobin formulation of the current disclosure isused at a rate that is less than about 75%, about 60%, about 50%, about40%, about 30%, about 20% or about 10% of the use rate (or the minimumuse rate of a range of use rates) listed on the label of a commerciallyavailable trifloxystrobin fungicide product. When used for plant healthapplications, the trifloxystrobin formulations of the present disclosurecan be used at active ingredient rates that correspond to any of thevalues or ranges of values noted above for the control of fungaldiseases on Cereals.

Trifloxystrobin—Cereals—Rice

Labelled use rates for the control of various fungal diseases of rice byGem™ a commercially trifloxystrobin fungicide, are provided in Table 13.

TABLE 13 Product Target Fungi Use Rate (g ai/ha) Gem ™ Sheath Blight(Rhizoctonia solani) 139-172 Rice Blast (Pyricularia grisea) 113-172

In some embodiments, the trifloxystrobin formulations of the currentdisclosure are used to control fungal diseases of rice at an activeingredient use rate that is lower than the use rate listed on the labelsof commercially available trifloxystrobin fungicides. In someembodiments, a trifloxystrobin formulation of the current disclosure isused to control fungal diseases of rice at a use rate that is less thanabout 75%, less than about 60%, less than about 50%, less than about40%, less than about 30%, less than about 20%, or less than about 10% ofa use rate listed on the label of a commercially availabletrifloxystrobin fungicide product.

In some embodiments, the trifloxystrobin formulations of the currentdisclosure are used to control fungal disease of rice at an activeingredient use rate that is lower than the minimum use rate of a rangeof use rates listed on the label of a commercially availabletrifloxystrobin product. In some embodiments a trifloxystrobinformulation of the current disclosure is used to control fungal diseaseat a use rate that is less than about 75%, less than about 60%, lessthan about 50%, less than about 40%, less than about 30%, less thanabout 20% or less than about 10% of the minimum use rate of a range ofuse rates listed on the label of a commercially availabletrifloxystrobin product.

In some embodiments, the trifloxystrobin formulations of the presentdisclosure may be used to control fungal diseases of rice at an activeingredient use rate of about 104-about 129 g/ha, about 83-about 103g/ha, about 69-about 86 g/ha, about 56-about 69 g/ha, about 42-about 51g/ha, about 28-about 34 g/ha or about 14-about 17 g/ha. In someembodiments, the trifloxystrobin formulations of the present disclosuremay be used to control fungal diseases of rice at an active ingredientuse rate of about 85-about 129 g/ha, about 68-about 103 g/ha, about57-about 86 g/ha, about 45-about 69 g/ha, about 34-about 51 g/ha, about23-about 34 g/ha or about 11-about 17 g/ha.

In some embodiments, the trifloxystrobin formulations of the presentdisclosure may be used to control fungal diseases of rice at an activeingredient use rate of less than about 104-about 129 g/ha, less thanabout 83 g/ha, less than about 69 g/ha, less than about 56 g/ha, lessthan about 42 g/ha, less than about 28 g/ha or less than about 14 g/ha.In some embodiments, the trifloxystrobin formulations of the presentdisclosure may be used to control fungal diseases of rice at an activeingredient use rate of less than about 85 g/ha, less than about 68 g/ha,less than about 57 g/ha, less than about 45 g/ha, less than about 34g/ha, less than about 23 g/ha or less than about 11 g/ha.

In some embodiments, the trifloxystrobin formulations of the currentdisclosure are used for plant health applications on rice at a use ratethat is lower than a use rate listed on the label of a commerciallyavailable trifloxystrobin fungicide product. In some embodiments, thetrifloxystrobin formulations of the current disclosure are used forplant health applications on rice at a use rate that is lower than theminimum use rate of a range of use rates listed on the label ofcommercially available trifloxystrobin fungicide product. In someembodiments, a trifloxystrobin formulation of the current disclosure isused at a rate that is less than about 75%, about 60%, about 50%, about40%, about 30%, about 20% or about 10% of the use rate (or the minimumuse rate of a range of use rates) listed on the label of a commerciallyavailable trifloxystrobin fungicide product. When used for plant healthapplications, the trifloxystrobin formulations of the present disclosurecan be used at active ingredient rates that correspond to any of thevalues or ranges of values noted above for the control of fungaldiseases on rice.

Trifloxystrobin—Cereals—Corn

In some embodiments, the trifloxystrobin formulations of the currentdisclosure are used to control fungal diseases of corn at an activeingredient use rate that is lower than the use rate listed on the labelsof commercially available trifloxystrobin fungicides. In someembodiments, a trifloxystrobin formulation of the current disclosure isused to control fungal diseases of corn at a use rate that is less thanabout 75%, less than about 60%, less than about 50%, less than about40%, less than about 30%, less than about 20%, or less than about 10% ofa use rate listed on the label of a commercially availabletrifloxystrobin fungicide product.

In some embodiments, the trifloxystrobin formulations of the currentdisclosure are used to control fungal disease of corn at an activeingredient use rate that is lower than the minimum use rate of a rangeof use rates listed on the label of a commercially availabletrifloxystrobin product. In some embodiments a trifloxystrobinformulation of the current disclosure is used to control fungal diseaseat a use rate that is less than about 75%, less than about 60%, lessthan about 50%, less than about 40%, less than about 30%, less thanabout 20% or less than about 10% of the minimum use rate of a range ofuse rates listed on the label of a commercially availabletrifloxystrobin product.

Examples of fungal diseases of corn that can be controlled withtrifloxystrobin of the present disclosure include but are not limited tovarious fungal diseases of corn noted in any other portion of thespecification.

In some embodiments, the trifloxystrobin formulations of the currentdisclosure are used for plant health applications on corn at a use ratethat is lower than a use rate listed on the label of a commerciallyavailable trifloxystrobin fungicide product. In some embodiments, thetrifloxystrobin formulations of the current disclosure are used forplant health applications on corn at a use rate that is lower than theminimum use rate of a range of use rates listed on the label ofcommercially available trifloxystrobin fungicide product. In someembodiments, a trifloxystrobin formulation of the current disclosure isused at a rate that is less than about 75%, about 60%, about 50%, about40%, about 30%, about 20% or about 10% of the use rate (or the minimumuse rate of a range of use rates) listed on the label of a commerciallyavailable trifloxystrobin fungicide product. When used for plant healthapplications, the trifloxystrobin formulations of the present disclosurecan be used at active ingredient rates that correspond to any of thevalues or ranges of values noted above for the control of fungaldiseases on corn.

Trifloxystrobin—Soybean

In some embodiments, the trifloxystrobin formulations of the currentdisclosure are used to control fungal diseases of soybean at an activeingredient use rate that is lower than the use rate listed on the labelsof commercially available trifloxystrobin fungicides. In someembodiments, a trifloxystrobin formulation of the current disclosure isused to control fungal diseases of soybean at a use rate that is lessthan about 75%, less than about 60%, less than about 50%, less thanabout 40%, less than about 30%, less than about 20%, or less than about10% of a use rate listed on the label of a commercially availabletrifloxystrobin fungicide product.

In some embodiments, the trifloxystrobin formulations of the currentdisclosure are used to control fungal disease of soybean at an activeingredient use rate that is lower than the minimum use rate of a rangeof use rates listed on the label of a commercially availabletrifloxystrobin product. In some embodiments a trifloxystrobinformulation of the current disclosure is used to control fungal diseaseat a use rate that is less than about 75%, less than about 60%, lessthan about 50%, less than about 40%, less than about 30%, less thanabout 20% or less than about 10% of the minimum use rate of a range ofuse rates listed on the label of a commercially availabletrifloxystrobin product.

Examples of fungal diseases of soybean and corresponding activeingredient use rates for their control can be found on the labels ofcommercially available trifloxystrobin fungicide products. Examples offungal diseases of soybean that can be controlled with formulations ofthe present disclosure include but are not limited to various fungaldiseases of soybean noted in any other portion of the specification.

In some embodiments, the trifloxystrobin formulations of the currentdisclosure are used for plant health applications on soybean at a userate that is lower than a use rate listed on the label of a commerciallyavailable trifloxystrobin fungicide product. In some embodiments, thetrifloxystrobin formulations of the current disclosure are used forplant health applications on soybean at a use rate that is lower thanthe minimum use rate of a range of use rates listed on the label ofcommercially available trifloxystrobin fungicide product. In someembodiments, a trifloxystrobin formulation of the current disclosure isused at a rate that is less than about 75%, about 60%, about 50%, about40%, about 30%, about 20% or about 10% of the use rate (or the minimumuse rate of a range of use rates) listed on the label of a commerciallyavailable trifloxystrobin fungicide product. When used for plant healthapplications, the trifloxystrobin formulations of the present disclosurecan be used at active ingredient rates that correspond to any of thevalues or ranges of values noted above for the control of fungaldiseases on soybean.

Trifloxystrobin—Pome Fruit

Labelled use rates for the control of various fungal diseases of PomeFruit by Flint® and Flint® 500 WG two commercially availabletrifloxystrobin wettable granule products are provided in Table 14.

TABLE 14 Use Rate (g ai/ Product Pome Fruits Labelled Target Fungi ha)Flint ® Apples, Pears, Scab (Venturia spp.) Preventative: 70 Crabapples,Loquat, Post-infection: 88 Mayhaw, Quince Cedar Apple Rust 70-88(Gymnosporangium juniperi-yirginianae), Powdery Mildew (Podosphaeraleucotricha), Powdery Mildew (Podosphaera leucotricha) Bitter Rot 105(Glomerella cingulata) White Rot (Botryosphaeria  53 dothidea) Flint ®Apples Scab (Venturia inaequalis) 37.5-60   500 WG

In some embodiments, the trifloxystrobin formulations of the currentdisclosure are used to control fungal diseases of pome fruits (includingbut not limited to apples, crabapples, pears, loquat, mayhaw, quince) atan active ingredient use rate that is lower than the use rate listed onthe labels of commercially available trifloxystrobin fungicides. In someembodiments, a trifloxystrobin formulation of the current disclosure isused to control fungal diseases of pome fruits at a use rate that isless than about 75%, less than about 60%, less than about 50%, less thanabout 40%, less than about 30%, less than about 20%, or less than about10% of a use rate listed on the label of a commercially availabletrifloxystrobin fungicide product.

In some embodiments, the trifloxystrobin formulations of the currentdisclosure are used to control fungal disease of pome fruits (includingbut not limited to apples, crabapples, pears, loquat, mayhaw, quince) atan active ingredient use rate that is lower than the minimum use rate ofa range of use rates listed on the label of a commercially availabletrifloxystrobin product. In some embodiments a trifloxystrobinformulation of the current disclosure is used to control fungal diseaseat a use rate that is less than about 75%, less than about 60%, lessthan about 50%, less than about 40%, less than about 30%, less thanabout 20% or less than about 10% of the minimum use rate of a range ofuse rates listed on the label of a commercially availabletrifloxystrobin product.

In some embodiments, the trifloxystrobin formulations of the presentdisclosure are used to control fungal diseases of pome fruits at anactive ingredient use rate of about 53-about 66 g/ha, about 42-about 53g/ha, about 35-about 44 g/ha, about 28-about 35 g/ha, about 21-about 26g/ha, about 14-about 18 g/ha or about 7-about 9 g/ha. In someembodiments, the trifloxystrobin formulations of the present disclosureare used to control fungal diseases of pome fruits at an activeingredient use rate of about 28-about 45 g/ha, about 22.5-about 36 g/ha,about 19-about 30 g/ha, about 15-about 24 g/ha, about 11-about 18 g/ha,about 7.5-about 12 g/ha or about 4-about 6 g/ha.

In some embodiments, the trifloxystrobin formulations of the presentdisclosure are used to control fungal diseases of pome fruits at anactive ingredient use rate of less than about 53 g/ha, less than about42 g/ha, less than about 35 g/ha, less than about 28 g/ha, less thanabout 21 g/ha, less than about 14 g/ha or less than about 7 g/ha. Insome embodiments, the trifloxystrobin formulations of the presentdisclosure are used to control fungal diseases of pome fruits at anactive ingredient use rate of less than about 28 g/ha, less than about22.5 g/ha, less than about 19 g/ha, less than about 15 24 g/ha, lessthan about 11 g/ha, less than about 7.5 g/ha or less than about 4 g/ha.

In some embodiments, the trifloxystrobin formulations of the currentdisclosure can be used to control fungal diseases of pome fruits at anactive ingredient use rate of less than about 39 g/ha, less than about32 g/ha, less than about 26 g/ha, less than about 21 g/ha, less thanabout 16 g/ha, less than about 11 g/ha, or less than about 5 g/ha. Insome embodiments, the trifloxystrobin formulations of the currentdisclosure can be used to control fungal diseases of pome fruits at anactive ingredient use rate of less than about 52.5 g/ha, less than about42 g/ha, less than about 35 g/ha, less than about 28 g/ha, less thanabout 21 g/ha, less than about 14 g/ha, or less than about 7 g/ha. Insome embodiments, the trifloxystrobin formulations of the currentdisclosure can be used to control fungal diseases of pome fruits at anactive ingredient use rate of less than about 66 g/ha, less than about53 g/ha, less than about 44 g/ha, less than about 35 g/ha, less thanabout 26 g/ha, less than about 18 g/ha, or less than about 9 g/ha. Insome embodiments, the trifloxystrobin formulations of the currentdisclosure can be used to control fungal diseases of pome fruits at anactive ingredient use rate of less than about 78 g/ha, less than about63 g/ha, less than about 53 g/ha, less than about 42 g/ha, less thanabout 32 g/ha, less than about 21 g/ha, or less than about 11 g/ha.

Non-limiting examples of fungal diseases of pome fruits that can becontrolled with trifloxystrobin formulations of the present disclosureinclude those listed in Table 14, above.

In some embodiments, the trifloxystrobin formulations of the currentdisclosure are used for plant health applications on pome fruit at a userate that is lower than a use rate listed on the label of a commerciallyavailable trifloxystrobin fungicide product. In some embodiments, thetrifloxystrobin formulations of the current disclosure are used forplant health applications on pome fruit at a use rate that is lower thanthe minimum use rate of a range of use rates listed on the label ofcommercially available trifloxystrobin fungicide product. In someembodiments, a trifloxystrobin formulation of the current disclosure isused at a rate that is less than about 75%, about 60%, about 50%, about40%, about 30%, about 20% or about 10% of the use rate (or the minimumuse rate of a range of use rates) listed on the label of a commerciallyavailable trifloxystrobin fungicide product. When used for plant healthapplications, the trifloxystrobin formulations of the present disclosurecan be used at active ingredient rates that correspond to any of thevalues or ranges of values noted above for the control of fungaldiseases on pome fruit.

Trifloxystrobin—Vine Fruits

In some embodiments, the trifloxystrobin formulations of the currentdisclosure are used to control fungal diseases of vine fruits (e.g.,strawberries, grapes) at an active ingredient use rate that is lowerthan the use rate listed on the labels of commercially availabletrifloxystrobin fungicides. In some embodiments, a trifloxystrobinformulation of the current disclosure is used to control fungal diseasesof vine fruits at a use rate that is less than about 75%, less thanabout 60%, less than about 50%, less than about 40%, less than about30%, less than about 20%, or less than about 10% of a use rate listed onthe label of a commercially available trifloxystrobin fungicide product.

In some embodiments, the trifloxystrobin formulations of the currentdisclosure are used to control fungal disease vine fruits (e.g.,strawberries, grapes) at an active ingredient use rate that is lowerthan the minimum use rate of a range of use rates listed on the label ofa commercially available trifloxystrobin product. In some embodiments atrifloxystrobin formulation of the current disclosure is used to controlfungal disease at a use rate that is less than about 75%, less thanabout 60%, less than about 50%, less than about 40%, less than about30%, less than about 20% or less than about 10% of the minimum use rateof a range of use rates listed on the label of a commercially availabletrifloxystrobin product.

Examples of fungal diseases of vine fruits corresponding activeingredient use rates for their control can be found on the labels ofcommercially available trifloxystrobin fungicide products.

In some embodiments, the trifloxystrobin formulations of the currentdisclosure are used for plant health applications on vine fruit at a userate that is lower than a use rate listed on the label of a commerciallyavailable trifloxystrobin fungicide product. In some embodiments, thetrifloxystrobin formulations of the current disclosure are used forplant health applications on vine fruit at a use rate that is lower thanthe minimum use rate of a range of use rates listed on the label ofcommercially available trifloxystrobin fungicide product. In someembodiments, a trifloxystrobin formulation of the current disclosure isused at a rate that is less than about 75%, about 60%, about 50%, about40%, about 30%, about 20% or about 10% of the use rate (or the minimumuse rate of a range of use rates) listed on the label of a commerciallyavailable trifloxystrobin fungicide product. When used for plant healthapplications, the trifloxystrobin formulations of the present disclosurecan be used at active ingredient rates that correspond to any of thevalues or ranges of values noted above for the control of fungaldiseases on vine fruits.

Trifloxystrobin—Vine Fruits—Grapes

Labelled use rates for the control of various fungal diseases of Grapesby Flint® and Flint® 500 WG a commercially available trifloxystrobinwettable granule product, are provided in Table 15.

TABLE 15 Product Target Fungi Use Rate (g ai/ha) Flint ® Powdery Mildew(Uncinula necator), 53, 70, 105 or 140 Botrytis Bunch Rot (Botrytiscinerea), depending on target Phomopsis Cane and Leaf Spot disease,disease (Phomopsis yiticolo), Black Rot pressure, application(Guignardia bidwellii), Downy Mildew interval etc. (Plasmopara yiticolo)

In some embodiments, the trifloxystrobin formulations of the currentdisclosure are used to control fungal diseases of grapes at an activeingredient use rate that is lower than the use rate listed on the labelsof commercially available trifloxystrobin fungicides. In someembodiments, a trifloxystrobin formulation of the current disclosure isused to control fungal diseases of grapes at a use rate that is lessthan about 75%, less than about 60%, less than about 50%, less thanabout 40%, less than about 30%, less than about 20%, or less than about10% of a use rate listed on the label of a commercially availabletrifloxystrobin fungicide product.

In some embodiments, the trifloxystrobin formulations of the currentdisclosure are used to control fungal disease grapes at an activeingredient use rate that is lower than the minimum use rate of a rangeof use rates listed on the label of a commercially availabletrifloxystrobin product. In some embodiments a trifloxystrobinformulation of the current disclosure is used to control fungal diseaseat a use rate that is less than about 75%, less than about 60%, lessthan about 50%, less than about 40%, less than about 30%, less thanabout 20% or less than about 10% of the minimum use rate of a range ofuse rates listed on the label of a commercially availabletrifloxystrobin product.

In some embodiments, the trifloxystrobin formulations of the currentdisclosure can be used to control fungal diseases of grapes an activeingredient use rate of about less than about 39 g/ha, less than about 32g/ha, less than about 26 g/ha, less than about 21 g/ha, less than about16 g/ha, less than about 11 g/ha, or less than about 5 g/ha. In someembodiments, the trifloxystrobin formulations of the current disclosurecan be used to control fungal diseases of grapes an active ingredientuse rate of less than about 53 g/ha, less than about 42 g/ha, less thanabout 35 g/ha, less than about 28 g/ha, less than about 21 g/ha, lessthan about 14 g/ha, or less than about 7 g/ha. In some embodiments, thetrifloxystrobin formulations of the current disclosure can be used tocontrol fungal diseases of grapes an active ingredient use rate of lessthan about 79 g/ha, less than about 63 g/ha, less than about 53 g/ha,less than about 42 g/ha, less than about 32 g/ha, less than about 21g/ha, or less than about 11 g/ha. In some embodiments, thetrifloxystrobin formulations of the current disclosure can be used tocontrol fungal diseases of grapes an active ingredient use rate of lessthan about 105 g/ha, less than about 84 g/ha, less than about 70 g/ha,less than about 56 g/ha, less than about 42 g/ha, less than about 28g/ha, or less than about 14 g/ha.

Non-limiting examples of fungal diseases of pome fruits that can becontrolled with trifloxystrobin formulations of the present disclosureinclude those listed in Table 15, above.

In some embodiments, the trifloxystrobin formulations of the currentdisclosure are used for plant health applications on grapes at a userate that is lower than a use rate listed on the label of a commerciallyavailable trifloxystrobin fungicide product. In some embodiments, thetrifloxystrobin formulations of the current disclosure are used forplant health applications on grapes at a use rate that is lower than theminimum use rate of a range of use rates listed on the label ofcommercially available trifloxystrobin fungicide product. In someembodiments, a trifloxystrobin formulation of the current disclosure isused at a rate that is less than about 75%, about 60%, about 50%, about40%, about 30%, about 20% or about 10% of the use rate (or the minimumuse rate of a range of use rates) listed on the label of a commerciallyavailable trifloxystrobin fungicide product. When used for plant healthapplications, the trifloxystrobin formulations of the present disclosurecan be used at active ingredient rates that correspond to any of thevalues or ranges of values noted above for the control of fungaldiseases on grapes.

Fluoxastrobin

In various embodiments, the fluoxastrobin formulations of the currentdisclosure may be used to control fungal diseases at active ingredientuse rates that are lower than the use rates listed on the labels ofcommercially available fluoxastrobin fungicides. In some embodiments, afluoxastrobin formulation of the current disclosure may be used tocontrol fungal disease at a use rate that is less than about 75%, lessthan about 60%, less than about 50%, less than about 40%, less thanabout 30%, less than about 20% or less than about 10% of a use ratelisted on the label of a commercially available fluoxastrobin fungicideproduct.

Labels of commercially available fluoxastrobin products often provideranges of active ingredient use rates to control certain fungal diseaseson certain plants (e.g., crops). In some embodiments, the fluoxastrobinformulations of the current disclosure are used to control fungaldisease at an active ingredient use rate that is lower than the minimumuse rate of a range of use rates listed on the label of a commerciallyavailable fluoxastrobin product. In some embodiments a fluoxastrobinformulation of the current disclosure is used to control fungal diseaseat a use rate that is less than about 75%, less than about 60%, lessthan about 50%, less than about 40%, less than about 30%, less thanabout 20% or less than about 10% of the minimum use rate of a range ofuse rates listed on the label of a commercially available product.

Fluoxastrobin—Cereals

In some embodiments, the fluoxastrobin formulations of the currentdisclosure are used to control fungal diseases of cereals at an activeingredient use rate that is lower than the use rate listed on the labelsof commercially available fluoxastrobin fungicides. In some embodiments,a fluoxastrobin formulation of the current disclosure is used to controlfungal diseases of cereals at a use rate that is less than about 75%,less than about 60%, less than about 50%, less than about 40%, less thanabout 30%, less than about 20%, or less than about 10% of a use ratelisted on the label of a commercially available fluoxastrobin fungicideproduct.

In some embodiments, the fluoxastrobin formulations of the currentdisclosure are used to control fungal disease of cereals at an activeingredient use rate that is lower than the minimum use rate of a rangeof use rates listed on the label of a commercially availablefluoxastrobin product. In some embodiments a fluoxastrobin formulationof the current disclosure is used to control fungal disease at a userate that is less than about 75%, less than about 60%, less than about50%, less than about 40%, less than about 30%, less than about 20% orless than about 10% of the minimum use rate of a range of use rateslisted on the label of a commercially available fluoxastrobin product.

Examples of fungal diseases of cereals and corresponding activeingredient use rates for their control can be found on the labels ofcommercially available fluoxastrobin fungicide products. Examples offungal diseases of cereals that can be controlled with formulations ofthe present disclosure include but are not limited to various fungaldiseases of cereals noted in any other portion of the specification.

In some embodiments, the fluoxastrobin formulations of the currentdisclosure are used for plant health applications on cereals at a userate that is lower than a use rate listed on the label of a commerciallyavailable fluoxastrobin fungicide product. In some embodiments, thefluoxastrobin formulations of the current disclosure are used for planthealth applications on cereals at a use rate that is lower than theminimum use rate of a range of use rates listed on the label ofcommercially available fluoxastrobin fungicide product. In someembodiments, a fluoxastrobin formulation of the current disclosure isused at a rate that is less than about 75%, about 60%, about 50%, about40%, about 30%, about 20% or about 10% of the use rate (or the minimumuse rate of a range of use rates) listed on the label of a commerciallyavailable fluoxastrobin fungicide product. When used for plant healthapplications, the fluoxastrobin formulations of the present disclosurecan be used at active ingredient rates that correspond to any of thevalues or ranges of values noted above for the control of fungaldiseases on cereals.

Picoxystrobin

In various embodiments, the picoxystrobin formulations of the currentdisclosure may be used to control fungal diseases at active ingredientuse rates that are lower than the use rates listed on the labels ofcommercially available picoxystrobin fungicides. In some embodiments, apicoxystrobin formulation of the current disclosure may be used tocontrol fungal disease at a use rate that is less than about 75%, lessthan about 60%, less than about 50%, less than about 40%, less thanabout 30%, less than about 20% or less than about 10% of a use ratelisted on the label of a commercially available picoxystrobin fungicideproduct.

Labels of commercially available picoxystrobin products often provideranges of active ingredient use rates to control certain fungal diseaseson certain plants (e.g., crops). In some embodiments, the picoxystrobinformulations of the current disclosure are used to control fungaldisease at an active ingredient use rate that is lower than the minimumuse rate of a range of use rates listed on the label of a commerciallyavailable picoxystrobin product. In some embodiments a picoxystrobinformulation of the current disclosure is used to control fungal diseaseat a use rate that is less than about 75%, less than about 60%, lessthan about 50%, less than about 40%, less than about 30%, less thanabout 20% or less than about 10% of the minimum use rate of a range ofuse rates listed on the label of a commercially available product.

Picoxystrobin—Soybean

Labelled use rates for the control of various fungal diseases of soybeanby Oranis® a commercially available picoxystrobin suspensionconcentrate, are provided in Table 16.

TABLE 16 Use Rate Product Target Fungi (g ai/ha) Oranis ® Phakopsorapachyrhizi, Cercospora kikuchii, 50-62.5 Septoria glycines

In some embodiments, the picoxystrobin formulations of the currentdisclosure are used to control fungal diseases of soybean at an activeingredient use rate that is lower than the use rate listed on the labelsof commercially available picoxystrobin fungicides. In some embodiments,a picoxystrobin formulation of the current disclosure is used to controlfungal diseases of soybean at a use rate that is less than about 75%,less than about 60%, less than about 50%, less than about 40%, less thanabout 30%, less than about 20%, or less than about 10% of a use ratelisted on the label of a commercially available picoxystrobin fungicideproduct.

In some embodiments, the picoxystrobin formulations of the currentdisclosure are used to control fungal disease of soybean at an activeingredient use rate that is lower than the minimum use rate of a rangeof use rates listed on the label of a commercially availablepicoxystrobin product. In some embodiments a picoxystrobin formulationof the current disclosure is used to control fungal disease at a userate that is less than about 75%, less than about 60%, less than about50%, less than about 40%, less than about 30%, less than about 20% orless than about 10% of the minimum use rate of a range of use rateslisted on the label of a commercially available picoxystrobin product.

In some embodiments, the picoxystrobin formulations of the presentdisclosure are used to control fungal diseases of soybean at an activeingredient use rate of about 37.5-about 50 g/ha, about 30-about 37.5g/ha, about 25-about 31 g/ha, about 20-about 25 g/ha, about 15-about 19g/ha, about 10-about 12.5 g/ha or about 5-about 6 g/ha.

In some embodiments, the picoxystrobin formulations of the presentdisclosure are used to control fungal diseases of soybean at an activeingredient use rate of less than about 37.5 g/ha, less than about 30g/ha, less than about 25 g/ha, less than about 20 g/ha, less than about15 g/ha, less than about 10 g/ha or less than about 5 g/ha.

Non-limiting examples of fungal diseases of soybeans that can becontrolled with picoxystrobin formulations of the present disclosureinclude those listed in Table 16, above.

In some embodiments, the picoxystrobin formulations of the currentdisclosure are used for plant health applications on soybean at a userate that is lower than a use rate listed on the label of a commerciallyavailable picoxystrobin fungicide product. In some embodiments, thepicoxystrobin formulations of the current disclosure are used for planthealth applications on soybean at a use rate that is lower than theminimum use rate of a range of use rates listed on the label ofcommercially available picoxystrobin fungicide product. In someembodiments, a picoxystrobin formulation of the current disclosure isused at a rate that is less than about 75%, about 60%, about 50%, about40%, about 30%, about 20% or about 10% of the use rate (or the minimumuse rate of a range of use rates) listed on the label of a commerciallyavailable picoxystrobin fungicide product. When used for plant healthapplications, the picoxystrobin formulations of the present disclosurecan be used at active ingredient rates that correspond to any of thevalues or ranges of values noted above for the control of fungaldiseases on soybean.

Picoxystrobin—Cereals

Labelled use rates for the control of various fungal diseases of cerealsby Acanto® a commercially available picoxystrobin suspensionconcentrate, are provided in Table 17.

TABLE 17 Use Rate Product Cereal Target Fungi (g ai/ha) Acanto ® WheatPowdery Mildew, 250 Septoria leaf and glume blotch,, Drechsleratritici-repentis-leaf blotch, Leaf Rust, Yellow Rust Barley PowderyMildew, net blotch, Leaf Spot 250 Disease, Dwarf Rust Rye PowderyMildew, Leaf Spot Disease, 250 Brown Rust Triticale Septoria-species 250

In some embodiments, the picoxystrobin formulations of the currentdisclosure are used to control fungal diseases of cereals at an activeingredient use rate that is lower than the use rate listed on the labelsof commercially available picoxystrobin fungicides. In some embodiments,a picoxystrobin formulation of the current disclosure is used to controlfungal diseases of cereals at a use rate that is less than about 75%,less than about 60%, less than about 50%, less than about 40%, less thanabout 30%, less than about 20%, or less than about 10% of a use ratelisted on the label of a commercially available picoxystrobin fungicideproduct.

In some embodiments, the picoxystrobin formulations of the currentdisclosure are used to control fungal disease of cereals at an activeingredient use rate that is lower than the minimum use rate of a rangeof use rates listed on the label of a commercially availablepicoxystrobin product. In some embodiments a picoxystrobin formulationof the current disclosure is used to control fungal disease at a userate that is less than about 75%, less than about 60%, less than about50%, less than about 40%, less than about 30%, less than about 20% orless than about 10% of the minimum use rate of a range of use rateslisted on the label of a commercially available picoxystrobin product.

In some embodiments, the picoxystrobin formulations of the presentdisclosure are used to control fungal diseases of cereals at an activeingredient use rate of less than about 187.5 g/ha, less than about 150g/ha, less than about 125 g/ha, less than about 100 g/ha, less thanabout 75 g/ha, less than about 50 g/ha or less than about 25 g/ha.

Non-limiting examples of fungal diseases of cereals that can becontrolled with picoxystrobin formulations of the present disclosureinclude those listed in Table 17, above.

In some embodiments, the picoxystrobin formulations of the currentdisclosure are used for plant health applications on cereals at a userate that is lower than a use rate listed on the label of a commerciallyavailable picoxystrobin fungicide product. In some embodiments, thepicoxystrobin formulations of the current disclosure are used for planthealth applications on cereals at a use rate that is lower than theminimum use rate of a range of use rates listed on the label ofcommercially available picoxystrobin fungicide product. In someembodiments, a picoxystrobin formulation of the current disclosure isused at a rate that is less than about 75%, about 60%, about 50%, about40%, about 30%, about 20% or about 10% of the use rate (or the minimumuse rate of a range of use rates) listed on the label of a commerciallyavailable picoxystrobin fungicide product. When used for plant healthapplications, the picoxystrobin formulations of the present disclosurecan be used at active ingredient rates that correspond to any of thevalues or ranges of values noted above for the control of fungaldiseases on cereals.

EXAMPLES

I: Preparation and Solid Formation of Nanoparticles ofPolymer-Associated Active Ingredients

Example 1: Preparation of 1 g of polymer nanoparticles from poly(methacrylic acid-co-ethyl acrylate) (p(MAA-co-EA))

1 g of polymer nanoparticles derived from p(MAA-co-EA) was made asfollows. Briefly, 1 g solid p(MAA-co-EA) (MAA:EA=90:10 or 80:20, MW450K-800K) was dissolved in 500 mL of deionized water in a 3 L beakerusing an overhead stirrer, and pH was maintained at {tilde over ( )}7with 1M NaOH. The solution was stirred overnight to fully dissolve thesolid. The next day, 500 mL of 3M NaCl was added to the solution undervigorous stirring. After addition, the solution was left to stir at 500rpm for another hour. At this stage, the solution viscosity dropsindicating the formation of collapsed polymers. The solution was thentransferred to a 3 L recrystallization dish equipped with a magneticstir bar. This solution was exposed to 4-254 nm UV germicidal lamps(G25T8) for 2 hours under constant stirring. After 2 hours, the solutionwas removed from the UV source and the ions were removed usingdiafiltration. The resulting retentate was then freeze dried to obtain apowder of the polymer nanoparticles. Alternatively, the retentate couldalso be spray dried to obtain a powder of the polymer nanoparticles. Aparticle size of 20-50 nm was measured via dynamic light scattering of asolution of either the collected freeze-dried or spray dried solidre-dispersed in 0.1M NaCl solution, pH adjusted to {tilde over ( )}6.8and stirred overnight.

The polarity of the microenvironment of the nanoparticles wasinvestigated according to the method outlined in Photochem. Photobiol.1982, 35:17. Briefly, 10 uL of a 0.1 mg/mL solution of pyrene in CH₂Cl₂was placed in a 20 ml scintillation vial and the liquid was swirledaround to coat the bottom of the vial. The solvent was allowed toevaporate under a fume hood. 10 ml of a 1 mg/mL dispersion of polymernanoparticles in deionized water (pH adjusted to {tilde over ( )}4.5)was added in to the vial with the dried out pyrene solution and wasstirred for 48 hours in the dark. Emission spectra were then measured ona Perkin Elmer LS 55 Luminescence Spectrometer using an excitationwavelength of 340 nm, having slit widths for both excitation andemission at 2.5 nm. The emission intensity of the first (I₁, ˜373 nm)and third (I₃, {tilde over ( )}384 nm) vibronic bands were recorded andthe ratio (I₁/I₃) calculated giving a ratio of {tilde over ( )}1.18indicating that the polymer nanoparticles prepared according to Example1 has a microenvironment similar to the polarity/hydrophobicity ofmethanol (see table in Photochem. Photobiol. 1982, 35:17 for a completetabulation of the ratios of I₁/I₃ and the corresponding microenvironmentpolarity.)

The same procedure was used to make polymer nanoparticles from differentpolyelectrolyte copolymers and polyelectrolyte homopolymers. Examples ofother polyelectrolyte copolymers: poly(methacrylic acid(MAA)-co-styrene(S)) (MAA:S=75:25, MW 450K-800K), poly(acrylic acid(AA)-co-styrene(S)) (AA:S=75:25, MW 450K-800K).

Example 2: Formation of a Solid Formulation of Nanoparticles orAggregates of Nanoparticles of Polymer-Associated Azoxystrobin Via SprayDrying Directly from Common Solvent Using p(MAA-Co-EA) Nanoparticles

5 g of polymer nanoparticles derived from p(MAA-co-EA) were madeaccording the procedure outlined in Example 1. The 5 g of polymer powderwas dispersed in 250 mL technical grade methanol in a 500 mL glassbeaker until a clear solution was formed, and was then filtered throughcoarse filter paper to remove any undispersed solids. 5 g of technicalgrade azoxystrobin was added to the filtered dispersion. The resultingsolution was clear, and was stirred at 500 rpm using a magnetic stir baron a stirrer hot plate for one hour. This solution was then spray driedon a Buchi mini Spray dryer B290 with inlet temperature set at 170° C.,aspirator gas flow rate of approximately 35 m³/h, feed rate ofapproximately 7 mL/min and air of flow 601 L/hr. The solid was collectedfrom the collector receptacle of the spray dryer. A volume averagedynamic light scattering (DLS) particle size of {tilde over ( )}300 nmwas measured for the solid re-dispersed either in deionized water orCIPAC D hard water at 400 ppm (solids). DLS particle size was measuredusing a Malvern Zetasizer ZS.

Example 3: Formation of a Solid Formulation of Nanoparticles orAggregates of Nanoparticles of Polymer-Associated Azoxystrobin from anAqueous Dispersion Using p(MAA-Co-EA) Polymer Nanoparticles

500 mg of polymer nanoparticles derived from p(MAA-co-EA) was madeaccording to the procedure outlined in Example 1. The solid wasdispersed in 25 mL technical grade methanol in a 50 mL glass beakeruntil a clear solution was formed, and was then filtered through coarsefilter paper to remove any undispersed solids. 500 mg of technical gradeazoxystrobin was then added to the filtered dispersion. The resultingsolution was clear, and was stirred at 500 rpm using a magnetic stir baron a stirrer hot plate for one hour. 0.250 L of deionized water was thenplaced in a 1 L glass beaker and was stirred at 500 rpm using anoverhead mixer. The methanol solution containing the nanoparticles andazoxystrobin was then slowly dripped into the stirred water at a rate of{tilde over ( )}1-2 mL/min using a peristaltic pump. After all themethanol has been added, the resulting milky solution was then left tomix for another 20 mins. The resulting solution was then freeze dried toobtain a solid formulation of azoxystrobin. The solid was redispersiblein water at a concentration of {tilde over ( )}200 ppm activeingredient. A volume average DLS particles size of {tilde over ( )}300nm was measured for the solid re-dispersed in deionized water at 400 ppmtotal solids in the measured dispersion. DLS particle size was measuredusing a Malvern Zetasizer ZS.

Example 4: Formation of a Solid Formulation of Nanoparticles orAggregates of Nanoparticles of Polymer-Associated Azoxystrobin from anAqueous Dispersion Using p(MAA-Co-EA) Polymer Nanoparticles at a 1:3Active to Polymer Ratio

500 mg of polymer nanoparticles derived from p(MAA-co-EA) was madeaccording to the procedure outlined in Example 1. The solid wasdispersed in 25 mL technical grade methanol in a 50 mL glass beakeruntil a clear solution was formed, and was then filtered through coarsefilter paper to remove any undispersed solids. 167 mg of technical gradeazoxystrobin was then added to the filtered dispersion. The resultingsolution was clear, and was stirred at 500 rpm using a magnetic stir baron a stirrer hot plate for one hour. 0.250 L of deionized water was thenplaced in a 1 L glass beaker and was stirred at 500 rpm using anoverhead mixer. The methanol solution containing the nanoparticles andazoxystrobin was then slowly dripped into the stirred water at a rate of{tilde over ( )}1-2 mL/min using a peristaltic pump. After all themethanol has been added, the resulting milky solution was then left tomix for another 20 mins. The resulting solution was then freeze dried toobtain a solid formulation of azoxystrobin. The solid was redispersiblein water at a concentration of {tilde over ( )}200 ppm activeingredient. A volume average DLS particles size of {tilde over ( )}300nm was measured for the solid re-dispersed in deionized water at 400 ppmtotal solids in the measured dispersion. DLS particle size was measuredusing a Malvern Zetasizer ZS.

Example 5: Formation of a Solid Formulation of Nanoparticles orAggregates of Nanoparticles of Polymer-Associated Azoxystrobin from anAqueous Dispersion Containing Phosphate Buffered Saline (PBS)

A 3% azoxystrobin solid formulation was made as follows: 300 mg ofpolymer nanoparticles derived from poly(acrylic acid (AA)-co-styrene(S))(AA:S=75:25 by mass, MW 450K-800K) was made according to the procedureoutlined in Example 1. The solid was dispersed in 15 mL technical grademethanol in a 50 mL glass beaker until a clear solution was formed, andwas then filtered through coarse filter paper to remove any undispersedsolids. 300 mg of technical grade azoxystrobin was then added to thefiltered dispersion. The resulting solution was clear, and was stirredat 500 rpm using a magnetic stir bar on a stirrer hot plate for onehour. 1 L of PBS buffer (Invitrogen, 1×, pH 7.4) was then placed in a 2L glass beaker and was stirred at 500 rpm using an overhead mixer. Themethanol solution containing the nanoparticles and azoxystrobin was thenslowly fed into the stirred buffer at a rate of {tilde over ( )}1-2mL/min using a peristaltic pump. The feeding tube was submerged underthe buffer during the entire addition process. After all the methanolhas been added, the resulting milky solution was then left to mix foranother 20 mins. The solution was then concentrated by removingwater/solvent using a rotary evaporator to about ½ its initial volume.The concentrated solution was then freeze dried to obtain a solidformulation of azoxystrobin. The solid was redispersible in water at aconcentration of {tilde over ( )}200 ppm active ingredient. A volumeaverage DLS particles size of {tilde over ( )}300 nm was measured forthe solid re-dispersed in deionized water at 400 ppm total solids in themeasured dispersion. DLS particle size was measured using a MalvernZetasizer ZS. Similar solid formulations were made using polymernanoparticles derived from poly(methacrylic acid (MAA)-co-styrene(S))(MAA:S=75:25, MW 450K-800K) and p(MAA-co-EA) (MAA:EA=90:10 or 80:20, MW450K-800K).

Example 6: Formation of a Solid Formulation of Nanoparticles orAggregates of Nanoparticles of Polymer-Associated Azoxystrobin from aDispersion Containing Phosphate Buffered Saline (PBS). [NanoparticlesDerived from p(AA-Co-S); 1:1 Ratio of Azoxystrobin:Nanoparticles]

A 5.4% azoxystrobin solid formulation was made as follows: Polymernanoparticles derived from poly(acrylic acid-co-styrene) (acrylicacid:styrene=75:25 by mass) were prepared according to the procedureoutlined in Example 1. 0.6 g of the polymer nanoparticles and 0.6 g oftechnical grade azoxystrobin were added to 30 mL of technical grademethanol in a 50 mL beaker. The resultant clear methanol mixture wasstirred for 30 minutes. The mixture was then added to 1170 g of 1×PBSbuffer (Phosphate Buffered Saline, 1×, Gibco) through a feed tube thatwas submerged in the PBS solution at a rate of 5 mL/min using aperistaltic pump. The PBS solution was stirred at 500 rpm throughout thecourse of the addition. The resulting mixture was cloudy/translucent inappearance. The mixture was freeze dried to give a solid. When thissolid was dispersed in RO water at a concentration of 200 ppm ofazoxystrobin, the Z-average DLS particle size was 416 nm. DLS particlesize was measured using a Malvern Zetasizer ZS.

Example 7: Formation of a Solid Formulation of Nanoparticles orAggregates of Nanoparticles of Polymer-Associated Azoxystrobin from anAqueous Dispersion Containing Phosphate Buffered Saline (PBS) at 3:2Polymer Nanoparticle:Azoxystrobin Ratio

A 3% azoxystrobin solid formulation was made as follows: 450 mg ofpolymer nanoparticles derived from poly(acrylic acid (AA)-co-styrene(S))(AA:S=75:25, MW 450K-800K) was made according to the procedure outlinedin Example 1. The solid was dispersed in 15 mL technical grade methanolin a 50 mL glass beaker until a clear solution was formed, and was thenfiltered through coarse filter paper to remove any undispersed solids.300 mg of technical grade azoxystrobin was then added to the filtereddispersion. The resulting solution was clear, and was stirred at 500 rpmusing a magnetic stir bar on a stirrer hot plate for one hour. 1 L ofPBS buffer (Invitrogen, 1×, pH 7.4) was then placed in a 2 L glassbeaker and was stirred at 500 rpm using an overhead mixer. The methanolsolution containing the nanoparticles and azoxystrobin was then slowlyfed into the stirred buffer at a rate of {tilde over ( )}1-2 mL/minusing a peristaltic pump. The feeding tube was submerged under thebuffer during the entire addition process. After all the methanol hasbeen added, the resulting milky solution was then left to mix foranother 20 mins. The resulting solution was then freeze dried to obtaina solid formulation of azoxystrobin. The solid was redispersible inwater at a concentration of {tilde over ( )}200 ppm active ingredient. Avolume average DLS particles size of {tilde over ( )}300 nm was measuredfor the solid re-dispersed in deionized water at 400 ppm total solids inthe measured dispersion. DLS particle size was measured using a MalvernZetasizer ZS.

Example 8: Formation of a Solid Formulation of Nanoparticles orAggregates of Nanoparticles of Polymer-Associated Azoxystrobin from anAqueous Dispersion Containing 0.05M NaCl Solution and a Dispersing Agent

A 40% azoxystrobin solid formulation was made as follows: 300 mg ofpolymer nanoparticles derived from poly(methacrylic acid(MAA)-co-styrene(S)) (MAA:S=75:25, MW 450K-800K) was made according tothe procedure outlined in Example 1. The solid was dispersed in 15 mLtechnical grade methanol in a 50 mL glass beaker until a clear solutionwas formed, and was then filtered through coarse filter paper to removeany undispersed solids. 300 mg of technical grade azoxystrobin was thenadded to the filtered dispersion. The resulting solution was clear, andwas stirred at 500 rpm using a magnetic stir bar on a stirrer hot platefor one hour. 1 L of deionized water was then placed in a 2 L glassbeaker and was stirred at 500 rpm using an overhead mixer. To this, 40mg of Soprophor BSU and 120 mg of NaCl was added. The methanol solutioncontaining the nanoparticles and azoxystrobin was then slowly fed intothe stirred buffer at a rate of {tilde over ( )}1-2 mL/min using aperistaltic pump. The feeding tube was submerged under the buffer duringthe entire addition process. After all the methanol has been added, theresulting milky solution was then left to mix for another 20 mins. Theresulting solution was then freeze dried to obtain a solid formulationof azoxystrobin. The solid was redispersible in water at a concentrationof {tilde over ( )}200 ppm active ingredient. A volume average DLSparticles size of {tilde over ( )}300 nm was measured for the solidre-dispersed in deionized water at 400 ppm total solids in the measureddispersion. DLS particle size was measured using a Malvern Zetasizer ZS.Similar solid formulations were made using polymer nanoparticles derivedfrom poly(acrylic acid (AA)-co-styrene(S)) (AA:S=75:25, MW 450K-800K)and p(MAA-co-EA) (MAA:EA=90:10 or 80:20, MW 450K-800K).

Example 9: Differential Scanning Calorimetry (DSC) Analysis of a SolidFormulation of Nanoparticles or Aggregates of Nanoparticles ofPolymer-Associated Azoxystrobin

Thermal analysis (DSC) was done using a Perkin Elmer DiamondDifferential Scanning calorimeter under N₂ atmosphere. The thermalbehavior of 6.05 mg of azoxystrobin was analyzed in an Aluminum samplepan from H2^(O) to 160° C. at a temperature ramp rate of 5° C./min.Similarly, the thermal behavior of 5.3 mg of a solid formulationprepared according to Example 4 was analyzed in an Aluminum pan from 25°C. to 160° C. at a temperature ramp rate of 5° C./min. Heat flow (mW/°C.) for both samples is shown in FIG. 1. No melting point is observedfor the solid formulation of azoxystrobin prepared according to Example4 compared to pure unformulated azoxystrobin which has an endothermic(melting) peak at 121° C.

II: Formulations

Example 10: Formation of a WP Formulation from an Aqueous Dispersion ofNanoparticles or Aggregates of Nanoparticles of Polymer-AssociatedAzoxystrobin

A 24% azoxystrobin solid formulation was made as follows: 500 mg ofpolymer nanoparticles derived from p(MAA-co-EA) was made according tothe procedure outlined in Example 1. The solid was dispersed in 25 mLtechnical grade methanol in a 50 mL glass beaker until a clear solutionwas formed, and was then filtered through coarse filter paper to removeany undispersed solids. 500 mg of technical grade azoxystrobin was thenadded to the filtered dispersion. The resulting solution was clear, andwas stirred at 500 rpm using a magnetic stir bar on a stirrer hot platefor one hour. 250 mL of deionized water was then placed in a 500 mLglass beaker and was stirred at 500 rpm using an overhead mixer. Tothis, 1.0 g of lactose, 30 mg of Reax88B, and 30 mg of Soprophor 4D 384were added. The methanol solution containing the polymer nanoparticlesand azoxystrobin was then slowly dripped into the water at a rate of{tilde over ( )}1-5 mL/min using a peristaltic pump. After all themethanol solution had been added, the resulting milky solution was thenleft to mix for another 20 mins. The solution was then concentrated byremoving solvent (both water and methanol) using a rotary evaporatoruntil {tilde over ( )}30-40% of the original volume was left. Theconcentrated mixture was freeze dried to obtain a dry powder. No visiblephase separation was observed in the solid after several freeze thawcycles (−5° C. to 45° C.). The cycled WP was redispersible in CIPAC-Dhard water and had a dispersed particle size of 300 nm at 200 ppm activeconcentration with native solution pH at 5.6. The same powder was madeusing nanoparticles derived from a homopolymer of acrylic acid (MW345K).

Example 11: Formation of a WP Formulation from an Aqueous Dispersion ofNanoparticles or Aggregates of Nanoparticles of Polymer-AssociatedAzoxystrobin. [Nanoparticles Derived from p(MAA-Co-S); 1:1 Ratio ofAzoxystrobin:Nanoparticles]

A 24% azoxystrobin solid formulation was made as follows: Polymernanoparticles derived from p(MAA-co-S) (MAA: S=75:25 by mass) wereprepared according to the procedure outlined in Example 1. 1.5 g of thepolymer nanoparticles and 1.5 g of technical grade azoxystrobin wereadded to 75 mL of technical grade methanol in a 150 mL beaker. Theresulting clear yellow mixture was stirred for 30 mins. 750 g RO water,3000 mg lactose, 90 mg Reax 88B and 90 mg Soprophor 4D384 were added toa 1 L beaker and the resulting aqueous solution was stirred at 500 rpmfor 30 minutes. The methanol mixture was then added to the aqueoussolution by means of a peristaltic pump at a rate of 5 mL/min though afeed tube submerged in the stirred aqueous solution. The aqueous mixturewas stirred at 500 rpm throughout the entire addition process. Afteraddition, the resulting mixture was cloudy/translucent and yellow inappearance. The resulting mixture was then freeze dried to give a solid.2.01 g of the freeze dried solid was mixed with 81 mg D-sorbitol using aspatula to form a homogenous powder. The solid mixture was placed in 2dram glass vial and was vortexed for 10 mins. When this solid wasdispersed in RO water at a concentration of 200 ppm azoxystrobin, theZ-average DLS particle was 186 nm. DLS particle size was measured usinga Malvern Zetasizer.

Example 12: Formation of a WP Formulation of Nanoparticles or Aggregatesof Nanoparticles of Polymer Associated Azoxystrobin. [NanoparticlesDerived from p(MAA-Co-S); 1:1 Ratio of Azoxystrobin:Nanoparticles] in aHigh Salt Solution

A 28% azoxystrobin solid formulation was made as follows: Polymernanoparticles derived from p(MAA-co-S) (MAA: S=75:25 by mass) wereprepared according to the procedure outlined in Example 1. 1.5 g of thepolymer nanoparticles and 1.5 g of technical grade azoxystrobin wereadded to 75 mL of technical grade methanol in a 150 mL beaker. Theresulting clear yellow mixture was stirred for 30 mins. 750 g RO water,90 mg Reax 88B and 12.5 mL NaCl (3M solution) were added to a 1 L beakerand the resulting aqueous solution was stirred at 500 RPM for 30 mins.The methanol mixture was then added to the aqueous mixture by means of aperistaltic pump at a rate of 5 mL/min though a feed tube submerged inthe stirred aqueous mixture. The aqueous mixture was stirred at 500 rpmthroughout the entire addition process. The resulting mixture wascloudy/translucent and yellow in appearance. The resulting mixture wasthen freeze dried to give a solid. When this solid was dispersed in ROwater at a concentration of 200 ppm azoxystrobin, the Z-average DLSparticle was 274 nm. DLS particle size was measured using a MalvernZetasizer ZS.

Example 13: Formation of WG Formulation from a Liquid Dispersion ofNanoparticles or Aggregates of Nanoparticles of Polymer-AssociatedAzoxystrobin

10 g of a solid formulation was prepared according to Example 3 usingp(MAA-co-EA). 10 g of the freeze-dried powder was then placed in abeaker. To this solid, about 2.5-3.0 of water was slowly added underconstant mixing until the resulting mixture had a dough-likeconsistency. The dough-like mixture was then extruded into 15 cm stripsthough the orifice of a 5 mL disposable hypodermic syringe. The extrudedstrips were allowed to dry for 1 hour and were then cut into 2-5 mmgranules. The WG formulation had minimal dustiness, and visible phaseseparation was observed in the solid after several freeze thaw cycles(−5° C. to 45° C.). The cycled WP was redispersible in CIPAC-D hardwater and had a dispersed particle size of 300 nm at 200 ppm activeconcentration. No phase separation of the active ingredient occurredafter several temperature cycles between 25° C. and 54° C.

Example 14: Preparation of a HSLS Formulation from a Solid Formulationof Nanoparticles or Aggregates of Nanoparticles of Polymer-AssociatedAzoxystrobin Via Ball-Milling [Nanoparticles Derived from p(MAA-Co-EA);3:1 Ratio of Azoxystrobin:Nanoparticles]

A 15% HSLS of azoxystrobin was prepared as follows. 1 g of polymernanoparticles derived from poly(MAA-co-EA) [MAA:EA=75:25 by mass;prepared according to Example 1] and 3 g of technical grade azoxystrobinwere added to 200 ml of methanol, and the resulting dispersion was spraydried according to the procedure outlined in Example 2. 1.5 g of theresulting spray dried powder was placed in a 16 mL brown glass vial(vial 1) along with 0.075 g Geropon T77, 0.375 g of Geropon TA/72 and 10g of stainless steel beads (20-30 mesh). The vial was covered, securedto a vortex, and shaken at 80% power for approximately 30 mins. 0.5025 gpropylene glycol, 0.3 g FG-10 (DOW® Corning, 10% active anti-foamingredient silicone emulsion), 0.02 g Proxel BD-20 (biocide, IndustrialMicrobiostat, 19.3% active biocide ingredient, Arch Chemicals Inc.), and4.69 g RO water were added into a separate 16 mL vial (vial 2). The vialwas covered, secured to a vortex, and shaken at 80% power forapproximately 30 mins. The contents of vial 2 were poured into vial 1.The resulting mixture was secured to a vortex and shaken at 80% powerfor 5 days. When the resulting formulation was diluted in RO water at aconcentration of 200 ppm azoxystrobin, the Z-average DLS particle sizewas 306 nm. DLS particle size was measured using a Malvern Zetasizer ZS.

Example 15: Preparation of a HSLS Formulation from a Solid Formulationof Nanoparticles or Aggregates of Nanoparticles of Polymer-AssociatedAzoxystrobin Via Ball-Milling [Nanoparticles Derived from p(MAA-Co-S);3:1 Ratio of Azoxystrobin:Nanoparticles]

A 15.7% HSLS of azoxystrobin was prepared as follows. 1 g of polymernanoparticles derived from derived from poly(MAA-co-S) [MAA:S=75:25 byweight] and 3 g of technical grade azoxystrobin were added to 200 mL ofmethanol, and the resulting dispersion was spray-dried according to theprocedure outlined in Example 2. 1.5 g of the resulting spray driedpowder was placed in a 16 mL brown glass vial (vial 1) along with 0.075g Geropon T77, 0.375 g of Geropon TA/72 and 10 g of stainless steelbeads (20-30 mesh). The vial was covered, secured to a vortex, andshaken at 80% power for approximately 30 mins. 0.5025 g propyleneglycol, 0.3 g FG-10 (DOW® Corning, 10% active anti-foam ingredientsilicone emulsion), 0.02 g Proxel BD-20 (biocide, IndustrialMicrobiostat, 19.3% active biocide ingredient, Arch Chemicals Inc.), and4.69 g RO water were added into a separate 16 mL vial (vial 2). The vialwas covered, secured to a vortex, and shaken at 80% power forapproximately 30 mins. The contents of vial 2 were poured into vial 1.The resulting mixture was secured on a vortex and shaken at 80% powerfor 5 days. When the resulting formulation was diluted in RO water at aconcentration of 200 ppm azoxystrobin, the Z-average DLS particle sizeis 351 nm. DLS particle size was measured using a Malvern Zetasizer ZS.

Example 16: Preparation of a HSLS Formulation from a Solid Formulationof Nanoparticles or Aggregates of Nanoparticles of Polymer-AssociatedAzoxystrobin Via Ball-Milling [Nanoparticles Derived fromp(MAA-Co-BUMA); 2:1 Ratio of Azoxystrobin:Nanoparticles]

A 16% HSLS of azoxystrobin was prepared as follows. 1 g of polymernanoparticles derived from derived from poly(MAA-co-BUMA)[MAA:BUMA=75:25 by weight; BUMA=Butyl methacrylate] and 2 g of technicalgrade azoxystrobin were added to 200 mL of methanol, and the resultingdispersion was spray-dried according to the procedure outlined inExample 2. 2 g of the resulting spray dried powder was placed in a 36 mLbrown glass vial (vial 1) along with 0.089 g Geropon T77, 0.445 g ofGeropon TA/72 and 10 g of stainless steel beads (20-30 mesh). The vialwas covered, secured to a vortex, and shaken at 80% power forapproximately 30 mins. 0.608 g propylene glycol, 0.362 g FG-10 (DOW®Corning, 10% active anti-foam ingredient silicone emulsion), 0.023 gProxel BD-20 (biocide, Industrial Microbiostat, 19.3% active biocideingredient, Arch Chemicals Inc.), 0.356 g Xanthan gum solution (5%aqueous Xanthan gum prepared form Kelzan® M, CP Kelco U.S., Inc.), and3.77 g RO (Reverse-osmosis purified) were added to a separate 36 mL vial(vial 2). The vial was covered, secured to a vortex, and shaken at 80%power for approximately 30 mins. The contents of vial 2 were poured intovial 1. The resulting mixture was secured on a vortex and shaken at 80%power for 2 days. When the resulting formulation was diluted in RO waterat a concentration of 200 ppm azoxystrobin, the Z-average DLS particlesize is 243 nm. DLS particle size was measured using a Malvern ZetasizerZS.

Example 17: Preparation of a HSLS Formulation from a Solid Formulationof Nanoparticles or Aggregates of Nanoparticles of Polymer-AssociatedAzoxystrobin Via Ball-Milling [Nanoparticles Derived from p(MAA-Co-EA);2:1 Ratio of Azoxystrobin:Nanoparticles]

A 15% HSLS of azoxystrobin was prepared as follows. 1 g of polymernanoparticles derived from derived from poly(MAA-co-EA) [MAA:EA=90:10 byweight] and 2 g of technical grade azoxystrobin were added to 200 mL ofmethanol, and the resulting dispersion was spray-dried according to theprocedure outlined in Example 2. 2 g of the resulting spray dried powderwas placed in a 36 mL brown glass vial (vial 1) along with 0.089 gGeropon T77, 0.445 g of Geropon TA/72, 1.482 g PVA (polyvinyl alcohol13-23K MW, Gohsenol) and 10 g of stainless steel beads (20-30 mesh). Thevial was covered, secured to a vortex, and shaken at 80% power forapproximately 30 mins. 0.596 g propylene glycol, 0.356 g FG-10 (DOW®Corning, 10% active anti-foam ingredient silicone emulsion), 0.023 gProxel BD-20 (biocide, Industrial Microbiostat, 19.3% active biocideingredient, Arch Chemicals Inc.), and 3.0 g RO (Reverse-osmosispurified) water were added into a separate 36 mL vial (vial 2). The vialwas covered, secured to a vortex, and shaken at 80% power forapproximately 30 mins. The contents of vial 2 were poured into vial 1.The resulting mixture was secured on a vortex and shaken at 80% powerfor 3 days. When the resulting formulation was diluted in RO water at aconcentration of 200 ppm azoxystrobin, the Z-average DLS particle sizeis 257 nm. DLS particle size was measured using a Malvern Zetasizer ZS.

Example 18: Preparation of a HSLS Formulation from a Solid Formulationof Nanoparticles or Aggregates of Nanoparticles of Polymer-AssociatedAzoxystrobin Via Ball-Milling [Nanoparticles Derived from p(MAA-Co-EA);4:1 Ratio of Azoxystrobin:Nanoparticles]

A 17% HSLS of azoxystrobin was prepared as follows. 1 g of polymernanoparticles derived from poly(MAA-co-EA) [MAA:EA=90:10 by weight,prepared according to Example 1] and 4 g of technical grade azoxystrobinwere added to 200 mL of methanol, and the resulting dispersion wasspray-dried according to the procedure outlined in example 2. 2 g of theresulting spray dried powder was placed in a 36 mL brown glass vial(vial 1) along with 0.107 g Geropon T77, 0.533 g of Geropon TA/72, 2.133g Silwet L-77 solution (10% aqueous solution) and 10 g of stainlesssteel beads (20-30 mesh). The vial was covered, secured to a vortex, andshaken at 80% power for approximately 30 mins. 0.715 g propylene glycol,0.427 g FG-10 (DOW® Corning, 10% active anti-foam ingredient siliconeemulsion), 0.031 g of Proxel BD-20 (biocide, Industrial Microbiostat,19.3% active biocide ingredient, Arch Chemicals Inc.), 0.436 g Xanthangum solution (5% aqueous Xanthan gum prepared form Kelzan® M, CP KelcoU.S., Inc.), and 4.5 g RO (Reverse-osmosis purified) water were addedinto a separate 36 mL vial (vial 2). The vial was covered, secured to avortex, and shaken at 80% power for approximately 30 mins. The contentsof vial 2 were poured into vial 1. The resulting mixture was secured ona vortex and shaken at 80% power for 4 days. When the resultingformulation was diluted in RO water at a concentration of 200 ppmazoxystrobin, the Z-average DLS particle size was 225 nm. DLS particlesize was measured using a Malvern Zetasizer ZS.

III Formulation Testing

Example 19: Lab-Scale Trial to Evaluate Translocation Properties ofAzoxystrobin Formulations of the Present Disclosure and CommerciallyAvailable Azoxystrobin Formulations in Corn

The translocation of azoxystrobin in formulations prepared according tothe present disclosure was compared to the commercially availableazoxystrobin formulation Amistar®. Dispersions of Amistar® and variousformulations of the present disclosure were prepared in 0.25 wt %Enhance solution (prepared in RO water) at azoxystrobin concentrationsof 200 or 500 ppm.

The following outlines the procedure for a single translocationexperiment:

Corn plants (corn variety: Sunnyvee) were planted and placed in a growthchamber. 12-16 days after planting, the basal region of the newest fullyemerged leaf of a corn plant was treated with an azoxystrobindispersion. Prior to treatment, the boundaries of the basal treatmentarea of the leaf were defined with a red paint pen. Ten 0.5 μL drops ofthe azoxystrobin formulation were then pipetted onto the upper surfaceof the basal treatment area (not on central vein). The drops were thenallowed to dry (drying is complete within 1 hour), and the plant wasplaced back into a growth chamber. The treated leaf was harvested 24hours later by cutting it at its base. The tip of the leaf was cut fromthe apical section (ca. 1.5 cm above the treatment boundary line),allowed to dry and placed in a glass vial. The dried leaf tips wereweighed, and the amount of azoxystrobin in the leaf tip was determinedby extracting the tip with 4 mL of acetone and quantifying the amount ofextracted active via HPLC.

Three replicate treatments were performed for each of the dispersionsinvestigated (reported values correspond to averages). Control leaftreatments of deionized water and de-ionized water+Enhance (0.25%) werealso performed

Table 18 and Table 19 demonstrate the translocation properties ofdispersions of various formulations at 200 and 500 ppm azoxystrobin,respectively.

TABLE 18 Results of translocation trials of several azoxystrobinformulations dispersed in 0.25 wt % Enhance solution at 200 ppmazoxystrobin. wt % (×10⁻³) azoxystrobin Treatment in leaf azoxystrobinin leaf Formulation Concentration (ppm) biomass (SD) biomass (μg) (SD)Amistar ® 200 2 (1) 0.12 (0.07) (have left these numbers because mightmerge tables later) Example 6 200 7 (1) 0.38 (0.04) Example 11 200 3 (1)0.27 (0.07) Example 12 200 5 (1) 0.4 (0.1) Example 14 200 3 (1) 0.21(0.03) SD = standard deviation (values in parentheses).

TABLE 19 Results of translocation trials of several formulationsdispersed 0.25 wt % Enhance solution at 500 ppm azoxystrobin. Treatmentwt % (×10⁻³) Concentration azoxystrobin in leaf azoxystrobin in leafFormulation (ppm) biomass (SD) biomass (μg) Amistar ® (control for 500(have 2 (1) 0.13 (0.05) Example 15, below) left these numbers becausemight merge tables later) Example 15 500 3 (2) 0.2 (0.1) Amistar ®(control for 500 1.1 (0.2) 0.09 (0.06) Example 16-Example 18, below)Example 16 500  4.8 (0.07) 0.21 (0.02) Example 17 500 3 (1) 0.2 (0.1)Example 18 500 2.4 (0.8) 0.12 (0.03) SD = standard deviation (values inparentheses).

Example 20: High-Salt Stability/Compatibility and of FormulationsPrepared According to the Present Disclosure

The redispersibiliy of azoxystrobin formulation of the presentdisclosure was tested by dispersing formulations prepared according toExample 15 and Example 17 in CIPAC H hard water (634 ppm hardness) at anactive ingredient concentration of 200 ppm. The formulations dispersedwell and were stable, with no signs of the formation of flocs. Whendispersed in CIPAC H hard water under these conditions, the Z-averageDLS particle size of the formulation of Example 15 was 237 nm, and thatof Example 17 was 450 nm. As described in other Examples, otherformulations of the present disclosure are redispersible solutions ofvarying hardness (e.g., other CIPAC standard waters).

Example 21: Stability Tests of Formulations of the Present Disclosure

The stability of formulations of the current disclosure preparedaccording to Example 15 and Example 17 was evaluated under two sets ofconditions. Briefly, formulations were kept in an environment chamber(Thermotron S-1.2C) for two weeks with alternating temperatures of −5°C. and 45° C. Each temperature was programmed for a 24-hour cyclingprocess. After the two-week temperature cycling process was complete,the formulations were redispersed in CIPAC H hard water (634 ppmhardness) at an active ingredient concentration of 200 ppm, and theZ-average particle size was measured by DLS. The formulations suspendedwell, with slightly increased particle size compared to measuredparticle sizes prior to cycling. The formulations were also maintainedat a constant temperature of 54° C. in an oven for one week, and thendispersed in CIPAC H water as described above. The formulationssuspended well, with slightly increased Z-average particle sizescompared to sizes prior to incubation at 54° C. As described in otherExamples, other formulations of the current disclosure are stable undera variety of test conditions (e.g., temperature cycling).

Example 22: Leaf Dip Bioassay to Test for Rainfastness of AzoxystrobinFormulations Prepared According to the Current Disclosure

The rainfastness of formulations of azoxystrobin prepared according tothe current disclosure and commercially available Amistar® was evaluatedvia a leaf dip assay.

1.7 cm leaf disks were cut from leaves of organically grown cabbage (ca.7 leaf stage) and were inoculated with dispersions prepared fromformulations of the present disclosure or Amistar. The inoculatingdispersions were prepared at 50 ppm azoxystrobin in an aqueous solutioncontaining 0.5% Supercharge Spray Adjuvant. Leaves were then dipped intothe inoculating dispersions for 5 seconds and then placed on a rack andallowed to air dry completely (1-2 hours) (No Rain). To test forrainfastness, some of the inoculated leaves were then dipped indeionized water for 5 seconds, and were allowed to air dry for 2 morehours (Rain treatment). The dried leaf tips were weighed, and the amountof azoxystrobin on the surface was determined by extracting the leaveswith 3 mL of acetone and quantifying the amount of extracted active viaHPLC.

Three replicate treatments were performed for each of the investigated(reported values correspond to averages). The results are presented inTable 20, with the amount of azoxystrobin reported as percentage drybiomass of the dried leaf. Control leaf treatments of deionized waterand de-ionized water+Supercharge (0.5%) were also performed.

The formulations of the current disclosure have are sufficientlyrainfast to retain azoxystrobin on the leaf after subjection to “Rain”conditions.

TABLE 20 Evaluation of rainfastness of azoxystrobin formulations wt %(×10⁻³) azoxystrobin in leaf Formulation Treatment Type biomass (SD)Amistar ® No Rain 14 (4) Rain 11 (3) Example 15 No Rain 11 (3) Rain 17(1) Example 16 No Rain 11 (1) Rain 21 (4) Example 17 No Rain 15 (7) Rain13 (1)

Example 23: Stability and Dispersibility of HSLS Formulations in CIPACG, H and J Standard Waters

HSLS formulations prepared according to Example 14, Example 15, Example16, Example 17 and Example 18 were dispersed in CIPAC G standard water(8000 ppm hardness, pH 6.0-7.0, Mg²⁺) at a concentration of 200 ppmazoxystrobin. The resulting dispersion were stable (no visibleaggregation/flocculation) for at least 1 hour. Dispersions preparedusing CIPAC H standard water (634 ppm hardness, pH6.0-7.0,Ca²⁺:Mg²⁺=2.5:1) and CIPAC J standard water (634 ppm hardness,pH6.0-7.0, Ca²⁺:Mg²⁺=2.5:1) also resulted in dispersions that werestable (no visible aggregation/flocculation) for at least an hour.

The invention claimed is:
 1. A liquid formulation comprising:nanoparticles comprising a polymer and a strobilurin compound with anaverage diameter of between about 1 nm and about 500 nm, wherein thepolymer is a polyelectrolyte copolymer comprised of between about 50weight percent and about 95 weight percent methacrylic acid monomers andbetween about 50 weight percent and about 5 weight percent ethylacrylate or styrene monomers and the strobilurin compound is associatedwith the polymer; between about 0.1 weight percent and about 1 weightpercent of an anti-foaming agent; between about 0.01 weight percent andabout 0.1 weight percent of a preservative; between about 0.5 weightpercent and about 5 weight percent of a naphthalene sulfonate condensatedispersant; and water; wherein the nanoparticles comprise between about5 weight percent and about 50 weight percent of the liquid formulation.2. The liquid formulation of claim 1, further comprising between about0.05 weight percent and about 10 weight percent of an anti-caking agentselected from the group consisting of attapulgite clay, sodiumaluminosilicate, silica, fumed silica, and combinations thereof.
 3. Theliquid formulation of claim 1, wherein the strobilurin compoundcomprises between about 5 weight percent and about 40 weight percent ofthe liquid formulation.
 4. The liquid formulation of claim 1, wherein aratio of a weight percent of the strobilurin compound to a weightpercent of the polymer is between about 1:1 and 5:1.
 5. The liquidformulation of claim 1, wherein the strobilurin compound is selectedfrom the group consisting of azoxystrobin, fluoxastrobin, picoxystrobin,pyraclostrobin, trifloxystrobin, enestrobin, famoxadone,metominostrobin, orysastrobin, kresoxim-methyl and combinations thereof.6. The liquid formulation of claim 1, further comprising an anti-freezeagent.
 7. The liquid formulation of claim 6, wherein the anti-freezeagent comprises between about 1 weight percent and about 10 weightpercent of the liquid formulation.
 8. The liquid formulation of claim 1,wherein the polyelectrolyte copolymer is a poly(methacrylicacid-co-ethyl acrylate) copolymer.
 9. The liquid formulation of claim 1,wherein the strobilurin compound has a melting point of less than 100°C.
 10. The liquid formulation of claim 1, wherein the liquid formulationlacks a UV-blocker.
 11. The liquid formulation of claim 1, furthercomprising a liquid fertilizer.
 12. The liquid formulation of claim 11,wherein the liquid fertilizer comprises at least one of the elementsselected from the group consisting of boron, copper, manganese, iron,chorine, molybdenum, zinc, sulfur, nitrogen, phosphorus and potassium.13. The liquid formulation of claim 1, wherein the polyelectrolytecopolymer is a poly(methacrylic acid-co-styrene) copolymer.
 14. Theliquid formulation of claim 1, wherein the polyelectrolyte copolymer iswater soluble at pH
 7. 15. The liquid formulation of claim 1, whereinthe polyelectrolyte copolymer has a water solubility at pH 7 of greaterthan 30%.
 16. A method of controlling fungal disease affecting a plantor anticipated to affect a plant, comprising applying the liquidformulation of claim 1 to a plant, a soil adjacent to a plant, or tosoil where a seed is or will be planted.
 17. The method of claim 16,wherein the liquid formulation further comprises between about 0.05weight percent and about 10 weight percent of an anti-caking agentselected from the group consisting of attapulgite clay, sodiumaluminosilicate, silica, fumed silica, and combinations thereof.
 18. Themethod of claim 16, wherein the liquid formulation further comprises ananti-freeze agent comprising between about 1 weight percent and about 10weight percent of the liquid formulation.